WEBVTT - Ep 87 C. diff: Fighting poop with poop

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<v Speaker 1>Hi, I'm Laney. So in August of twenty nineteen, I

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<v Speaker 1>started having wild bowel movements. That's about the only way

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<v Speaker 1>that I can put it. I have celiac. I have

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<v Speaker 1>irritable bowel. And these stools were nothing like I had

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<v Speaker 1>ever encountered before. They were coming every hour to half

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<v Speaker 1>an hour. Seemed like I couldn't be more than ten

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<v Speaker 1>feet from my bathroom at any given time. I went

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<v Speaker 1>to our little local first daid station kind of at

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<v Speaker 1>my husband's job, and they had medical staff, and I said, look,

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<v Speaker 1>something's not right, it's not okay. I intentionally withheld the

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<v Speaker 1>fact that I had celiac disease, knowing that a lot

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<v Speaker 1>of doctors actually like to just hang their hat on

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<v Speaker 1>any GI symptom. And at the very end she had

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<v Speaker 1>had gone through everything was gonna just basically say, if

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<v Speaker 1>it's still not okay in a couple of days, come back.

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<v Speaker 1>And somehow the word got out that I had celiac disease.

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<v Speaker 1>And she said, oh, you must have just had gluten,

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<v Speaker 1>that's all. And even though I was sure, she said,

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<v Speaker 1>have some bananas, drink lots of water. Your stool should

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<v Speaker 1>firm up and everything will be fine, and all I

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<v Speaker 1>really wanted to do was go to my normal GP,

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<v Speaker 1>but in rural Iowa, he was over an hour away

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<v Speaker 1>and I could not make that trip to save my life.

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<v Speaker 1>No bathrooms on the way, no gas stations. It would

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<v Speaker 1>have been like me in a cornfield, So not an option. Finally,

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<v Speaker 1>when I was having what I would consider a good day,

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<v Speaker 1>I called my doctor and I said, I'm on my way,

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<v Speaker 1>I need to come see you, and he submitted a

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<v Speaker 1>test for SEDIFF. Sure enough, I came back positive. From there,

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<v Speaker 1>we went through basically the standard first steps and I

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<v Speaker 1>was put on a course of metronitisolar flagile. I saw

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<v Speaker 1>a little improvement, but once the course of antibiotics was finished,

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<v Speaker 1>it was all right back. So then he called in

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<v Speaker 1>oral Vancomyasin. Thankfully that cleared it up. After the fact,

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<v Speaker 1>we were trying to do a little research on how

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<v Speaker 1>I acquired my seat of infection, and it wasn't until

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<v Speaker 1>it was a long thought, afterthought that I had a

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<v Speaker 1>bug bite before that and it had gotten infected and

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<v Speaker 1>they had put me on superflexis in about two months prior.

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<v Speaker 1>Fast forwarding to March of twenty twenty one, I am

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<v Speaker 1>a vet tech and it was my third week on

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<v Speaker 1>the job, we were still doing curbside because of COVID.

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<v Speaker 1>I went out to go get a dog to bring

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<v Speaker 1>it into the hospital. Somehow the dogs muscle slipped off

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<v Speaker 1>when the owner was placing its lead on it, lunched

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<v Speaker 1>at me, tackled me into a snow bank, and I

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<v Speaker 1>had puncture wounds in my arm and had to go

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<v Speaker 1>seek medical attention, where they put me on clintamyasin and zyperflexisin.

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<v Speaker 1>I mentioned to urgent care, I have a history of cediff.

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<v Speaker 1>Please help me. That's not what we should be doing.

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<v Speaker 1>And instead of her directions for having a yogurt every day,

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<v Speaker 1>she suggested a take to have two yogurts every day.

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<v Speaker 1>That was a little insulting, to say the least. A

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<v Speaker 1>few days later, my armhead absessed. I went to my

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<v Speaker 1>current doctor's emergency room. I went in and they said,

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<v Speaker 1>we need to admit you to the hospital. They started

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<v Speaker 1>me on ivy vankamyasin, ivy metronitisol and ivy is trianam,

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<v Speaker 1>which is a pretty kind of novel antibiotic that they

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<v Speaker 1>only use in real serious cases. From there, my bite

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<v Speaker 1>moom cleaned up. I was messaging my doctor like every day,

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<v Speaker 1>at least a couple times a day, freaking out about

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<v Speaker 1>having sea diiff again, sure that I was probably going

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<v Speaker 1>to have it again, and he agreed that I was

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<v Speaker 1>probably going to have seediff again from all of these antibiotics. Finally,

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<v Speaker 1>when I was discharged from the hospital three days later,

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<v Speaker 1>they don't have an oral version of as tree and am,

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<v Speaker 1>so they put me on leva floxis, in another broad

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<v Speaker 1>spectrum antibiotic. My heart kind of sank, knowing what the

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<v Speaker 1>future held. It was about ten days after I was

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<v Speaker 1>home from the hospital, had gone back to work, those

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<v Speaker 1>urgent loose tools that when you feel it you need

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<v Speaker 1>to sprint to the bathroom, but don't spread too fast.

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<v Speaker 1>And I called my doctor and I said, look, I

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<v Speaker 1>think I've got sea diiff. He ordered the test. I

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<v Speaker 1>came down and I positive for SEEDFF. So they started

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<v Speaker 1>me on oral vank commiasin right away, and finally, after

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<v Speaker 1>it was a month on the bank commosin and doing

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<v Speaker 1>a taper, things were starting to kind of finally feel normal.

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<v Speaker 1>I finished my antibiotics and it wasn't three days later

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<v Speaker 1>before I was at work and I realized, in the

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<v Speaker 1>last hour and a half I've gone to the bathroom

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<v Speaker 1>three times. I messaged my doctor while I was at work.

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<v Speaker 1>I said, I need another test. I don't think it's gone,

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<v Speaker 1>And sure enough I went over our lunch break, I

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<v Speaker 1>took a longer lunch than we normally have and went

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<v Speaker 1>down and by the time we were done. That night

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<v Speaker 1>at work, I had my results that I had seediff again.

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<v Speaker 1>I had a recurren seed if infection. That meant my

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<v Speaker 1>doctor was calling infectious disease specialists and I spoke to

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<v Speaker 1>infectious disease specialists and they referred me immediately to you

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<v Speaker 1>a research trial for fecal transplant. They didn't even want

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<v Speaker 1>to see me and they just sent me straight there.

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<v Speaker 1>Then I get the phone call and I tell them

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<v Speaker 1>my story. They said, you absolutely qualify for a fecal

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<v Speaker 1>transplant with your recurrent infection. Will schedule you for. It

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<v Speaker 1>was June thirtieth. It was my transplant date, and I

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<v Speaker 1>had it circled and like starred on a calendar, but

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<v Speaker 1>it was still a month out. So it was exhilarating

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<v Speaker 1>but also a nerving knowing that I had to deal

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<v Speaker 1>with this infection. So we started another Vincimizon taper. I

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<v Speaker 1>stayed on the dose that basically kept my stools solid.

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<v Speaker 1>From there, I waited until my transplant date. My transplant

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<v Speaker 1>was colon ascapy guided, so they did a colonoscopy and

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<v Speaker 1>then they came in and applied the fecal transplant matter.

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<v Speaker 1>I remember wheeling it in to the colon ass could

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<v Speaker 1>be room and seeing a jar with brown liquid in it,

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<v Speaker 1>and I took a selfie with it. I was so excited.

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<v Speaker 1>I screamed, that's my poop, that's my new poop, and

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<v Speaker 1>the doctors laughed at me. I was just so excited. Thankfully,

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<v Speaker 1>post transplant, things are going well. I have post infectious

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<v Speaker 1>irritable bewel, probably on top of normal irritable bell, but

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<v Speaker 1>they're still calling it post infection. So day to day

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<v Speaker 1>life things are going pretty well. However, every time I

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<v Speaker 1>feel like a little gas bubble or I get a

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<v Speaker 1>funny little cramp, my heart sinks and I'm worried that

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<v Speaker 1>the seed off his back because the doctors did notify

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<v Speaker 1>me that my infection was relatively severe and that I

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<v Speaker 1>might have to kind of get what they call little

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<v Speaker 1>tune ups as far as just additional fecal transplants in

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<v Speaker 1>the future, and so every time I get a funny

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<v Speaker 1>little feeling I'm instantly worried, and my doctor even associates

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<v Speaker 1>that with a little bit of PTSD. Honestly, from the

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<v Speaker 1>whole event, it's interesting to think that I have more

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<v Speaker 1>trauma from the medical fallout from my dog bite than

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<v Speaker 1>the actual dog bite itself. Seed Iff has really stuck

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<v Speaker 1>with me for anyone who's comparing it, because my mom

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<v Speaker 1>was trying to put a label on it. She was saying,

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<v Speaker 1>it can't be worse than kolonoscopy prep. It can't be

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<v Speaker 1>worse than kolonoscopy prep. And I can officially say, after

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<v Speaker 1>doing both that seed Iff is much worse.

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<v Speaker 2>Wow.

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<v Speaker 3>Thank you so much, Laney for taking the time to

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<v Speaker 3>share your story with us. That's intense.

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<v Speaker 4>Yeah, wow, thank you.

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<v Speaker 1>Hi.

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<v Speaker 3>I'm Erin Welsh and I'm Erin Alman Updike and this

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<v Speaker 3>is this podcast will kill you.

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<v Speaker 2>Welcome everyone.

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<v Speaker 4>We're excited about this episode.

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<v Speaker 3>As we are about all our episodes. It's genuine excitement.

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<v Speaker 4>It always is.

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<v Speaker 2>Today we're talking about Claustridium difficile a ka se diff Seediff.

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<v Speaker 3>That's how I'm going to talk about it for the

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<v Speaker 3>of the episode. But we're not talking just about this

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<v Speaker 3>problematic pathogen. We're also talking about one of my favorite

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<v Speaker 3>solutions to infection.

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<v Speaker 2>Yeah, one of my favorite solutions to a problem.

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<v Speaker 3>Yeah, yeah, I simply love it. And of course we

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<v Speaker 3>are talking about fecal microbiota transplantation.

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<v Speaker 2>Aka fecal transplant. We have talked about this like, we've

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<v Speaker 2>dabbled in it and several other episodes and been like ooh, someday, ooh, someday,

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<v Speaker 2>that day.

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<v Speaker 4>Is finally here everyone.

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<v Speaker 3>Yes, this is not going to be like a full

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<v Speaker 3>takedown of the microbiome and all the impact that it

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<v Speaker 3>has on different conditions or whatever in this associations, but

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<v Speaker 3>we are going to do somewhat of a deep dive

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<v Speaker 3>into fecal transplants or fmts, and we are very excited

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<v Speaker 3>to bring on a special guest, an expert guest, to

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<v Speaker 3>help us out with that. But that's jumping way ahead

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<v Speaker 3>of ourselves.

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<v Speaker 2>It is because first, it's quarantine.

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<v Speaker 3>Any time, it is what are we drinking this week?

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<v Speaker 2>This week we're drinking the slurry?

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<v Speaker 3>This We're sorry is that when everyone wants to drink? Okay,

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<v Speaker 3>So the thing is, it was either make a gross

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<v Speaker 3>recipe or a gross name and not both and so

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<v Speaker 3>one or the other had to happen. But yeah, exactly,

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<v Speaker 3>I mean, like we are but human. So what is

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<v Speaker 3>in the slurry? This?

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<v Speaker 2>The slurry contains mango, pineapple, lime, tamarind, and tequila, all

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<v Speaker 2>delicious things. And of course you gotta blend it up.

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<v Speaker 3>You got to. You gotta blend it up. But it

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<v Speaker 3>tastes good, right, and it's like yeah, so.

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<v Speaker 2>I mean, it's like very fruity. It's a lot of flavors.

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<v Speaker 2>We promise it's worth it.

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<v Speaker 3>Yeah, yeah, And we will post the full recipe for

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<v Speaker 3>this slurry quarantine as well as the non alcoholic place

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<v Speaker 3>sy Burrita on our website this podcast will Kill You

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<v Speaker 3>dot com, as well as on all of our social

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<v Speaker 3>media channels.

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<v Speaker 2>Yes, we will, Aaron, What other business should we tell

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<v Speaker 2>everyone about?

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<v Speaker 3>Well, how about our website? Okay, it's my turn to

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<v Speaker 3>do the rundown of things on there. I'm nervous.

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<v Speaker 4>You can do it. I believe in you.

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<v Speaker 3>Okay, here we go. We have all of our references

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<v Speaker 3>to all of our episodes on each episode page. We

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<v Speaker 3>have transcripts. We have links to our bookshop dot org

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<v Speaker 3>affiliate page, and our good Raids list. We have links

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<v Speaker 3>to music Bloodmobile now on Spotify. We have links to

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<v Speaker 3>our merch which we have very incredible merch.

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<v Speaker 4>Please check it out.

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<v Speaker 3>And we have a pro code page. I mean, I

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<v Speaker 3>think that's that's got to be most of the things

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<v Speaker 3>on there.

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<v Speaker 2>It's most of the things. Definitely check it out. This

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<v Speaker 2>podcast will kill You dot com. So does that mean

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<v Speaker 2>we're ready to talk about C DIFF?

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<v Speaker 1>Yeah?

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<v Speaker 3>I think I think so. Thanks also to everyone who

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<v Speaker 3>has requested this over the years. Yeah, and we hope

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<v Speaker 3>you liked the episode.

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<v Speaker 2>Yeah, so let's get right into it after this break.

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<v Speaker 1>So.

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<v Speaker 2>I don't know if anyone but me would notice this,

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<v Speaker 2>but I think it's funny. I'm going to start this

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<v Speaker 2>episode almost identically to Anthrax. I think, oh our Anthrax episode.

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<v Speaker 3>I don't remember this, so this is good.

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<v Speaker 2>It's fine, nobody will. But as I was typing it,

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<v Speaker 2>I was like, this sounds familiar. And then I opened

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<v Speaker 2>my Anthrax notes and I was like, ah, okay. Claustridium

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<v Speaker 2>difficile infection is caused by an anaerobic gram positive rod

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<v Speaker 2>shaped spore forming toxin producing bacterium.

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<v Speaker 4>Yeah.

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<v Speaker 3>Hold on, okay, a quick question already already?

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<v Speaker 4>What then is that? Also?

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<v Speaker 3>How you started the botulism episode.

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<v Speaker 2>Ooh, probably, yeah, probably, Okay, I genuinely forgot that we

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<v Speaker 2>ever did botulism erin.

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<v Speaker 4>It was a long time ago.

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<v Speaker 3>I loved that. I loved that it was.

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<v Speaker 4>A good episode. I forgot.

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<v Speaker 2>It'll also be probably the way that I start tetanus

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<v Speaker 2>whenever we do that, so, you know, So for the

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<v Speaker 2>remainder of this episode, like we said, I'm probably just

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<v Speaker 2>gonna refer to this as sea diff because it's easier

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<v Speaker 2>and shorter, and that's how I'm we're gonna say it. So,

0:15:11.640 --> 0:15:17.200
<v Speaker 2>sea diff causes an infection that most of the time,

0:15:17.560 --> 0:15:21.920
<v Speaker 2>very commonly is what's called a nosocomial infection, which means

0:15:22.040 --> 0:15:27.440
<v Speaker 2>hospital or healthcare acquired. So the way that I've tried

0:15:27.520 --> 0:15:32.360
<v Speaker 2>to organize this biology section is to first focus on

0:15:32.480 --> 0:15:37.320
<v Speaker 2>the disease that Clusterdium difficiale can cause, how it's transmitted,

0:15:37.400 --> 0:15:40.120
<v Speaker 2>how it makes us sick, and then take kind of

0:15:40.160 --> 0:15:42.760
<v Speaker 2>a bigger picture view and talk a little bit about

0:15:42.760 --> 0:15:45.680
<v Speaker 2>the microbiome as it relates to sea diff infection.

0:15:46.320 --> 0:15:48.640
<v Speaker 4>Because as a spoiler.

0:15:48.600 --> 0:15:52.320
<v Speaker 2>That Aaron, I know, you probably already know, and many

0:15:52.400 --> 0:15:58.760
<v Speaker 2>listeners may know, but se diff doesn't always or necessarily

0:15:59.520 --> 0:16:00.520
<v Speaker 2>cause infection.

0:16:01.520 --> 0:16:04.360
<v Speaker 3>Yeah, it's it's like, uh, it's got to be one

0:16:04.400 --> 0:16:10.280
<v Speaker 3>of our first besides MRSA maybe like opportunistic super opportunistic pathogens.

0:16:10.480 --> 0:16:13.560
<v Speaker 2>Yeah, we haven't covered a lot of opportunistic pathogens on here.

0:16:13.720 --> 0:16:17.520
<v Speaker 2>This is definitely one of them, but we'll get there eventually.

0:16:18.400 --> 0:16:22.120
<v Speaker 2>First of all, transmission of sea diff at like the

0:16:22.120 --> 0:16:25.760
<v Speaker 2>most basic level. The way that anyone in the world

0:16:25.800 --> 0:16:27.920
<v Speaker 2>gets exposed to sea diff in the first place is

0:16:28.080 --> 0:16:32.800
<v Speaker 2>fecal oral so poop in mouth. It's a common mode

0:16:32.800 --> 0:16:38.120
<v Speaker 2>of transmission, especially for GI bacteria, and sea diff, like

0:16:38.160 --> 0:16:41.880
<v Speaker 2>I mentioned, is a spore forming bacterium like our friend

0:16:42.000 --> 0:16:49.440
<v Speaker 2>Bascillas anthrasis and Clusterdium tetani and also Botulinum and clusterdrium bochculainum. Anyways,

0:16:50.000 --> 0:16:54.560
<v Speaker 2>see diff is also an anaerobic bacterium. Like a lot

0:16:54.640 --> 0:16:59.560
<v Speaker 2>of our gut bacteria are either entirely or facultatively anaerobic,

0:17:00.000 --> 0:17:03.200
<v Speaker 2>which means that they survive without oxygen. So what happens

0:17:03.240 --> 0:17:06.359
<v Speaker 2>in the case of seedff is that on contact with oxygen,

0:17:06.600 --> 0:17:10.960
<v Speaker 2>like when we poop out this bacterium, it forms spores,

0:17:11.480 --> 0:17:16.919
<v Speaker 2>and these spores are very highly environmentally resistant inactive forms

0:17:16.960 --> 0:17:21.240
<v Speaker 2>of this bacteria. They really can't easily be killed by

0:17:21.240 --> 0:17:25.560
<v Speaker 2>heat or cold or alcohol, and they can persist in

0:17:25.640 --> 0:17:30.119
<v Speaker 2>the environment, not dying or desiccating, just hanging out until

0:17:30.160 --> 0:17:34.680
<v Speaker 2>they're ingested by another human or animal, because animals can

0:17:34.720 --> 0:17:35.640
<v Speaker 2>also get infected.

0:17:36.119 --> 0:17:38.120
<v Speaker 4>And then once we ingest them.

0:17:38.160 --> 0:17:42.000
<v Speaker 2>These spores can easily survive the acidic environment of our stomach,

0:17:42.440 --> 0:17:47.440
<v Speaker 2>travel through our guts, and then these spores are activated

0:17:47.560 --> 0:17:50.320
<v Speaker 2>in our small or large intestine when they come into

0:17:50.359 --> 0:17:52.600
<v Speaker 2>contact with our bile acids.

0:17:53.240 --> 0:17:55.360
<v Speaker 4>Hmm, isn't that fascinating?

0:17:56.320 --> 0:17:58.840
<v Speaker 3>Yeah, okay, I have a question about how long these

0:17:58.880 --> 0:17:59.879
<v Speaker 3>spores can last.

0:18:00.080 --> 0:18:01.080
<v Speaker 4>Oh, good question.

0:18:01.400 --> 0:18:03.800
<v Speaker 2>I don't have an exact timeline, but definitely on the

0:18:03.880 --> 0:18:06.679
<v Speaker 2>order of months, possibly years, depending on the conditions.

0:18:07.040 --> 0:18:11.720
<v Speaker 3>I really hate that about these things. Yeah, it's very

0:18:11.800 --> 0:18:15.119
<v Speaker 3>It makes it very scary and like it feels a

0:18:15.119 --> 0:18:17.480
<v Speaker 3>bit challenging.

0:18:17.880 --> 0:18:19.800
<v Speaker 4>Oh, very very challenging.

0:18:21.080 --> 0:18:21.480
<v Speaker 1>Huh.

0:18:21.480 --> 0:18:24.720
<v Speaker 3>Okay, So the bile acids, like, what about them?

0:18:25.240 --> 0:18:25.440
<v Speaker 5>Yeah?

0:18:25.480 --> 0:18:27.360
<v Speaker 3>What is bile acid I'm.

0:18:27.200 --> 0:18:28.560
<v Speaker 4>So glad that you asked, Arin.

0:18:28.760 --> 0:18:34.400
<v Speaker 2>Let me tell you so. Bile acids are basically cholesterol derivatives.

0:18:34.520 --> 0:18:40.360
<v Speaker 2>Our liver makes bile and secretes it into our gallbladder

0:18:40.400 --> 0:18:44.040
<v Speaker 2>where it's like stored, and then whenever you eat something,

0:18:44.119 --> 0:18:47.200
<v Speaker 2>it sends signals to our gall butter to contract squeeze

0:18:47.240 --> 0:18:50.640
<v Speaker 2>out the bile and that goes into our small intestine.

0:18:50.720 --> 0:18:54.800
<v Speaker 2>And these bile acids help support digestion, especially the digestion

0:18:54.960 --> 0:18:56.720
<v Speaker 2>and eventual absorption.

0:18:56.400 --> 0:18:58.800
<v Speaker 3>Of fats huh okay.

0:18:58.960 --> 0:19:02.720
<v Speaker 2>And it's a little bit more complicated. There's like multiple

0:19:02.800 --> 0:19:05.920
<v Speaker 2>kinds of bile acids, and they're converted in our small

0:19:05.920 --> 0:19:09.959
<v Speaker 2>intestine from like primary into secondary. And it seems like

0:19:10.320 --> 0:19:13.560
<v Speaker 2>when sea diff spores come into contact with some types

0:19:13.600 --> 0:19:17.320
<v Speaker 2>of these bio acids, especially in higher concentrations, that's when

0:19:17.359 --> 0:19:22.880
<v Speaker 2>they very easily reactivate into a live, replicatable, mobile sea

0:19:22.920 --> 0:19:28.440
<v Speaker 2>diff bacteria, which can then replicate and replicate and kind

0:19:28.480 --> 0:19:34.880
<v Speaker 2>of beat out other bacteria in our guts and eventually

0:19:34.880 --> 0:19:35.560
<v Speaker 2>cause infection.

0:19:36.560 --> 0:19:43.360
<v Speaker 3>Are there other bacteria that are activated or inactivated by

0:19:43.600 --> 0:19:46.480
<v Speaker 3>biole like do the bile acids kill a lot of

0:19:46.520 --> 0:19:50.879
<v Speaker 3>potentially food born bacteria or are other food born bacteria

0:19:51.560 --> 0:19:53.400
<v Speaker 3>resistant to bio acids.

0:19:53.560 --> 0:19:56.679
<v Speaker 2>That's a good question I don't fully know the answer to,

0:19:57.680 --> 0:19:59.320
<v Speaker 2>but I'm going to put a pin in it because

0:19:59.359 --> 0:20:01.720
<v Speaker 2>I want to kind of get back to bio acids

0:20:01.760 --> 0:20:09.040
<v Speaker 2>in a minute, okay, as it relates to our gut microbiome. Okay,

0:20:09.359 --> 0:20:13.640
<v Speaker 2>So now the spores are activated, sea diff is replicating,

0:20:14.080 --> 0:20:17.680
<v Speaker 2>and then somehow this leads to disease.

0:20:18.800 --> 0:20:21.360
<v Speaker 4>How you may ask Aaron if you wanted to.

0:20:22.600 --> 0:20:26.840
<v Speaker 2>I do okay, good, okay. Some species of sea diff.

0:20:27.359 --> 0:20:31.600
<v Speaker 2>Not only do they form these spores in adverse conditions,

0:20:31.640 --> 0:20:35.479
<v Speaker 2>but they also have the ability to produce toxins. And

0:20:35.520 --> 0:20:40.480
<v Speaker 2>it turns out that it's these toxins, not the bacteria themselves,

0:20:40.800 --> 0:20:46.120
<v Speaker 2>that are capable of causing infection aka sea diff colitis.

0:20:46.800 --> 0:20:52.960
<v Speaker 2>So let's talk about what that actually looks like. Predominantly,

0:20:53.800 --> 0:20:57.679
<v Speaker 2>se diff the toxogenic strains, the strains that produce toxins

0:20:58.280 --> 0:21:03.159
<v Speaker 2>produce two major talks, very creatively named toxin A and

0:21:03.200 --> 0:21:07.840
<v Speaker 2>toxin B. Keeps it easy, and essentially, what these two

0:21:07.960 --> 0:21:13.080
<v Speaker 2>toxins do is they work together to ultimately disrupt the

0:21:13.280 --> 0:21:18.280
<v Speaker 2>membranes of the cells that line your gut, and this

0:21:18.440 --> 0:21:22.240
<v Speaker 2>results in little micro ulcerations of our gut wall, little

0:21:22.280 --> 0:21:26.720
<v Speaker 2>little holes. It also disrupts the junction between cells which

0:21:26.720 --> 0:21:29.359
<v Speaker 2>are supposed to be you know, a nice tight line

0:21:29.400 --> 0:21:33.720
<v Speaker 2>of cells lining our gut. Basically, these toxins get in

0:21:33.760 --> 0:21:38.040
<v Speaker 2>there and kind of shred the lining between them, leaving holes,

0:21:38.640 --> 0:21:43.240
<v Speaker 2>which increases permeability, and that is what leads to watery,

0:21:43.600 --> 0:21:50.560
<v Speaker 2>massive amounts of diarrhea. These toxins also then induce apoptosis

0:21:50.840 --> 0:21:54.200
<v Speaker 2>and kill the cells that line our gut wall because

0:21:54.200 --> 0:21:57.000
<v Speaker 2>of all of this disruption, and that leads to a

0:21:57.040 --> 0:22:00.320
<v Speaker 2>lot of inflammation that can cause the formation of what

0:22:00.359 --> 0:22:04.840
<v Speaker 2>are called pseudo membranes, which sounds gross and it looks gross.

0:22:05.600 --> 0:22:06.600
<v Speaker 4>It's essentially just.

0:22:06.680 --> 0:22:11.040
<v Speaker 2>Hordes of these dead cells mixed with bacteria and white

0:22:11.080 --> 0:22:15.159
<v Speaker 2>blood cells and inflammatory gunk, and it forms this kind

0:22:15.200 --> 0:22:18.959
<v Speaker 2>of membrane that then lines your gut, which even further

0:22:19.720 --> 0:22:24.080
<v Speaker 2>prevents your colon from doing its job right of absorbing water,

0:22:24.320 --> 0:22:28.080
<v Speaker 2>et cetera, which then leads to even more diarrhea.

0:22:28.720 --> 0:22:32.800
<v Speaker 3>Okay, so I'm assuming that the benefit that seaediff gets

0:22:33.040 --> 0:22:36.520
<v Speaker 3>from these toxins is that it can sort of wipe

0:22:36.520 --> 0:22:40.400
<v Speaker 3>out the competition and even further and colonize as much

0:22:40.400 --> 0:22:42.760
<v Speaker 3>as it wants to your intestines.

0:22:43.680 --> 0:22:44.800
<v Speaker 4>Yeah, that's a good question.

0:22:45.840 --> 0:22:49.679
<v Speaker 2>Maybe probably, I would guess, though, I mean, certainly it

0:22:49.720 --> 0:22:52.720
<v Speaker 2>makes it hard for anything else to exist. Where these

0:22:52.720 --> 0:22:54.240
<v Speaker 2>pseudo membranes exist.

0:22:54.600 --> 0:22:58.200
<v Speaker 3>Okay, so it might not be necessarily helping with the colonization,

0:22:58.280 --> 0:23:00.600
<v Speaker 3>but it helps clear the competition.

0:23:01.520 --> 0:23:04.639
<v Speaker 2>Yeah, it's interesting because sea diiff is actually not a

0:23:04.760 --> 0:23:08.920
<v Speaker 2>very good competitor to begin with, right, whether whether it's

0:23:08.960 --> 0:23:14.520
<v Speaker 2>toxogenic or non toxogenic. So maybe these toxins are helping

0:23:14.520 --> 0:23:16.800
<v Speaker 2>a little bit and making it a little bit more competitive.

0:23:17.240 --> 0:23:18.240
<v Speaker 2>But I don't know for sure.

0:23:19.240 --> 0:23:24.320
<v Speaker 3>Okay, toxins are costly to make m H, so you

0:23:24.320 --> 0:23:28.080
<v Speaker 3>would think there'd be some sort of benefit from well toxins.

0:23:28.160 --> 0:23:29.960
<v Speaker 2>I mean kind of like we've talked about in a

0:23:29.960 --> 0:23:34.800
<v Speaker 2>lot of our bacterial pathogens that cause diarrhea. People who

0:23:35.040 --> 0:23:38.600
<v Speaker 2>are having massive watery diarrhea because of sea diiff are

0:23:38.600 --> 0:23:44.760
<v Speaker 2>spreading billions of spores, and spores, yeah, are very environmentally hardy,

0:23:44.880 --> 0:23:48.640
<v Speaker 2>and so perhaps that's the major advantage, is that you're

0:23:48.680 --> 0:23:53.000
<v Speaker 2>able to spread. Okay, I don't know if it's that satisfying,

0:23:53.080 --> 0:24:02.680
<v Speaker 2>but but that's kind of the main and result. There's

0:24:02.720 --> 0:24:05.320
<v Speaker 2>a lot more detail on these toxins. They're very interesting.

0:24:05.480 --> 0:24:09.200
<v Speaker 2>There's also another toxin that is present in some strains

0:24:09.200 --> 0:24:15.359
<v Speaker 2>that seems to when its present cause even more severe disease. Uh,

0:24:15.960 --> 0:24:18.240
<v Speaker 2>But I'm not going to get into all of the

0:24:18.480 --> 0:24:22.800
<v Speaker 2>specific biochemistry of it, because there's a lot more that

0:24:22.840 --> 0:24:26.199
<v Speaker 2>I want to talk about with zetiff. But the end

0:24:26.320 --> 0:24:30.240
<v Speaker 2>result of these toxins and the disruption that they cause

0:24:30.280 --> 0:24:32.840
<v Speaker 2>in the lining of our colon, the death that they

0:24:32.920 --> 0:24:35.280
<v Speaker 2>cause of the cells that line our colon, and all

0:24:35.359 --> 0:24:39.720
<v Speaker 2>of this inflammation is what really causes the symptoms that

0:24:39.760 --> 0:24:40.320
<v Speaker 2>we see.

0:24:40.880 --> 0:24:45.240
<v Speaker 3>Is it only the toxogenic strains that cause disease?

0:24:45.480 --> 0:24:45.840
<v Speaker 4>Okay?

0:24:45.920 --> 0:24:48.359
<v Speaker 2>Yeah, And there are a lot of studies looking at

0:24:48.760 --> 0:24:51.200
<v Speaker 2>do you have to have both of these toxins because

0:24:51.240 --> 0:24:53.640
<v Speaker 2>it's toxin A and toxin B or could you have

0:24:53.800 --> 0:24:57.280
<v Speaker 2>just one of these toxins. There's still some question as

0:24:57.359 --> 0:25:00.920
<v Speaker 2>to that. It seems like in some models or in

0:25:00.960 --> 0:25:05.600
<v Speaker 2>some clinical studies, they've seen that strains that only produce

0:25:05.640 --> 0:25:10.199
<v Speaker 2>toxin B can still cause disease, so a might be

0:25:10.280 --> 0:25:14.640
<v Speaker 2>kind of like a benefit but not necessary to cause disease.

0:25:14.880 --> 0:25:17.080
<v Speaker 2>But then in other studies it looks like, no, you

0:25:17.160 --> 0:25:18.960
<v Speaker 2>really have to have both, and if you only have

0:25:19.040 --> 0:25:22.440
<v Speaker 2>one or the other, you don't really see disease from

0:25:22.520 --> 0:25:26.520
<v Speaker 2>sea diiff, even though you might have colonization. So it's

0:25:26.520 --> 0:25:28.200
<v Speaker 2>still a little bit I think up in the air.

0:25:28.280 --> 0:25:30.960
<v Speaker 2>But it is really interesting the way that these two

0:25:31.119 --> 0:25:34.800
<v Speaker 2>toxins kind of interact to then cause the actual symptoms

0:25:35.160 --> 0:25:39.120
<v Speaker 2>that we see. Okay, so I've said the word symptoms

0:25:39.119 --> 0:25:40.760
<v Speaker 2>like one hundred times, but I think the only thing

0:25:40.800 --> 0:25:44.120
<v Speaker 2>I've said so far is diarrhea, and that is the

0:25:44.160 --> 0:25:50.119
<v Speaker 2>hallmark symptom of a sea diiff infection, massive watery maybe

0:25:50.240 --> 0:25:55.960
<v Speaker 2>mucis diarrhea. Generally, it's not overtly bloody diarrhea like we

0:25:56.040 --> 0:26:00.840
<v Speaker 2>see with dysentery, and that's largely because seadift doesn't invade

0:26:01.119 --> 0:26:03.840
<v Speaker 2>through our cells and it's very rare that it causes

0:26:03.880 --> 0:26:07.920
<v Speaker 2>disease outside of the intestine. But because it is causing

0:26:07.960 --> 0:26:11.480
<v Speaker 2>all of this inflammation and this damage to the lining

0:26:11.520 --> 0:26:14.840
<v Speaker 2>of our gut, you can see like micro amounts of

0:26:14.880 --> 0:26:19.320
<v Speaker 2>blood in the diarrhea, but usually not like what would

0:26:19.400 --> 0:26:25.680
<v Speaker 2>look like bloody diarrhea. And otherwise symptoms can really really range.

0:26:26.040 --> 0:26:28.960
<v Speaker 2>You can have very mild diarrhea with a set off

0:26:28.960 --> 0:26:34.600
<v Speaker 2>infection to severe life threatening colitis that is the inflammation

0:26:34.760 --> 0:26:38.840
<v Speaker 2>of your colon, of your gut wall. And even though

0:26:38.880 --> 0:26:41.919
<v Speaker 2>it doesn't usually go outside of our colon and cause

0:26:42.000 --> 0:26:45.480
<v Speaker 2>actual infection anywhere else. It can generate such a strong

0:26:45.680 --> 0:26:48.320
<v Speaker 2>inflammatory response in our body that you see a lot

0:26:48.359 --> 0:26:52.000
<v Speaker 2>of other signs of infectionate inflammation, a lot of abdominal

0:26:52.040 --> 0:26:59.560
<v Speaker 2>pain with this infection, fevers, nausea, vomiting, generalized weakness because

0:27:00.160 --> 0:27:04.040
<v Speaker 2>you're having diarrhea of all of your anything you're trying

0:27:04.040 --> 0:27:08.280
<v Speaker 2>to eat, and so in severe cases, if this goes untreated,

0:27:08.280 --> 0:27:11.920
<v Speaker 2>it can lead to significant dehydration, which can then lead

0:27:11.960 --> 0:27:16.000
<v Speaker 2>to shock and death. It can also lead to something

0:27:16.040 --> 0:27:20.639
<v Speaker 2>called toxic mega colon, which sounds horrific and talked about

0:27:21.280 --> 0:27:24.240
<v Speaker 2>I think we have on shagus ah.

0:27:24.200 --> 0:27:24.800
<v Speaker 4>Was it shaugus?

0:27:24.920 --> 0:27:25.120
<v Speaker 1>Yep.

0:27:25.800 --> 0:27:29.639
<v Speaker 2>Essentially, toxic mega colon is where your colon gets so inflamed.

0:27:29.880 --> 0:27:32.840
<v Speaker 2>It's a very different mechanism here than in shagas disease,

0:27:33.680 --> 0:27:37.000
<v Speaker 2>but it becomes very very distended and is unable to

0:27:37.160 --> 0:27:40.040
<v Speaker 2>move any contents down your gut the way that it's

0:27:40.040 --> 0:27:43.960
<v Speaker 2>supposed to, so gas and fecal contents just keep building up,

0:27:44.000 --> 0:27:46.760
<v Speaker 2>and that can lead to perforation of your bells, which

0:27:46.840 --> 0:27:48.840
<v Speaker 2>is of course a life threatening emergency.

0:27:49.240 --> 0:27:49.520
<v Speaker 1>Yeah.

0:27:49.600 --> 0:27:52.560
<v Speaker 3>I mean all of this sounds not only like painful

0:27:52.600 --> 0:27:57.080
<v Speaker 3>and really unpleasant, but very life threatening.

0:27:57.520 --> 0:27:58.240
<v Speaker 4>Very Yeah.

0:27:58.280 --> 0:28:01.960
<v Speaker 2>So the mortality rate direct due to sea diiff infection

0:28:02.240 --> 0:28:06.560
<v Speaker 2>is estimated to be about five percent, but that's just

0:28:06.640 --> 0:28:11.840
<v Speaker 2>for death directly due to seedff infection, So sea diff

0:28:11.880 --> 0:28:16.440
<v Speaker 2>colitis causing death. If you look at overall mortality that's

0:28:16.560 --> 0:28:22.639
<v Speaker 2>associated with sea diff infection, which includes like downstream complications,

0:28:22.840 --> 0:28:26.720
<v Speaker 2>but also just the fact that a large proportion of

0:28:26.760 --> 0:28:30.600
<v Speaker 2>people who get sea diff infection are often already sick

0:28:30.600 --> 0:28:35.200
<v Speaker 2>with underlying conditions, and so the kind of associated mortality

0:28:35.280 --> 0:28:38.280
<v Speaker 2>rate is often up to fifteen to twenty five percent,

0:28:39.320 --> 0:28:41.360
<v Speaker 2>Or if you look at people who are already in

0:28:41.400 --> 0:28:44.640
<v Speaker 2>the ICU, so already like very sick, it's up to

0:28:44.680 --> 0:28:47.720
<v Speaker 2>like thirty percent, which is horrific.

0:28:48.280 --> 0:28:51.880
<v Speaker 3>Yeah, yeah, yeah and scary.

0:28:52.360 --> 0:28:55.480
<v Speaker 2>It's really really scary. Yeah, sea diff is like the

0:28:55.600 --> 0:28:57.040
<v Speaker 2>scourge of hospitals.

0:28:58.480 --> 0:29:00.520
<v Speaker 4>But like I said.

0:29:00.400 --> 0:29:03.600
<v Speaker 2>At the top, as severe as the infection that sea

0:29:03.640 --> 0:29:08.200
<v Speaker 2>diiff causes can be, it doesn't always make us sick.

0:29:08.440 --> 0:29:12.400
<v Speaker 2>It's an opportunistic pathogen and aarin. You'll probably talk more

0:29:12.400 --> 0:29:14.400
<v Speaker 2>about this in the history section, So I hope I'm

0:29:14.440 --> 0:29:18.800
<v Speaker 2>not stepping on your toes, but Claustridium difficile was actually

0:29:18.880 --> 0:29:22.000
<v Speaker 2>first identified as just like a normal component of the

0:29:22.040 --> 0:29:28.200
<v Speaker 2>microbiome in a healthy infants and neonates, what like, yeah, yeah,

0:29:28.440 --> 0:29:31.920
<v Speaker 2>so this is a bacterium that might exist in me,

0:29:32.240 --> 0:29:35.560
<v Speaker 2>or you, aaron, or in quite a lot of you listening,

0:29:35.800 --> 0:29:38.200
<v Speaker 2>just as one of the I don't know how many

0:29:38.360 --> 0:29:44.040
<v Speaker 2>hundreds of species happily coexist inside of our gut microbiome. Right,

0:29:44.880 --> 0:29:48.760
<v Speaker 2>So then the question becomes who gets sick from sea

0:29:48.800 --> 0:29:52.920
<v Speaker 2>diff and who lives with sea diff without ever getting

0:29:52.960 --> 0:29:59.920
<v Speaker 2>sick and why? And the answer relates to two major things,

0:30:00.240 --> 0:30:03.479
<v Speaker 2>one of which we've kind of already touched on. So

0:30:03.680 --> 0:30:08.240
<v Speaker 2>first and most obviously, is is this a toxin producing

0:30:08.280 --> 0:30:11.720
<v Speaker 2>strain or not? So not all strains of sea diiff

0:30:11.800 --> 0:30:15.080
<v Speaker 2>produce those toxins. And because it's the toxins and not

0:30:15.200 --> 0:30:20.840
<v Speaker 2>the bacterium that causes the damage, if you are colonized

0:30:20.840 --> 0:30:24.760
<v Speaker 2>with a non toxogenic strain, you're very unlikely to get

0:30:24.840 --> 0:30:29.120
<v Speaker 2>sea diiff colitis or seadiff infection. And there's actually some

0:30:29.240 --> 0:30:32.200
<v Speaker 2>interesting studies, and I think this might be a little

0:30:32.200 --> 0:30:35.280
<v Speaker 2>bit controversial because there just isn't a ton of data

0:30:35.320 --> 0:30:40.160
<v Speaker 2>on it where they separate non toxogenic from toxogenic strains.

0:30:40.880 --> 0:30:44.520
<v Speaker 2>But the data that does exist suggests that if you're

0:30:44.560 --> 0:30:48.360
<v Speaker 2>colonized with a non toxogenic strain, it might actually be

0:30:48.440 --> 0:30:53.840
<v Speaker 2>protective against infection with a toxogenic strain. But what's interesting

0:30:54.200 --> 0:30:58.920
<v Speaker 2>is it doesn't seem to be an immune mediated response necessarily.

0:30:59.240 --> 0:31:00.760
<v Speaker 3>Oh so it's like competition.

0:31:01.120 --> 0:31:03.160
<v Speaker 4>Uh huh, let's talk about it a little more.

0:31:03.400 --> 0:31:05.160
<v Speaker 3>I mean, does that just have to do with like

0:31:05.880 --> 0:31:10.160
<v Speaker 3>the fact that it's a bad competitor and it's so

0:31:10.400 --> 0:31:12.200
<v Speaker 3>needs like an open playing field.

0:31:12.520 --> 0:31:12.880
<v Speaker 4>Yeah.

0:31:12.920 --> 0:31:17.080
<v Speaker 2>So the other major thing other than strain that affects

0:31:17.120 --> 0:31:23.560
<v Speaker 2>whether somebody gets Claustridium difficile infection or just is colonized

0:31:23.600 --> 0:31:28.280
<v Speaker 2>with sea diff or has neither, like doesn't get seadiff

0:31:28.320 --> 0:31:33.040
<v Speaker 2>infection and isn't colonized with sea diff is their microbiome

0:31:33.920 --> 0:31:38.600
<v Speaker 2>and the composition of their microbiome to begin with. So

0:31:38.840 --> 0:31:40.680
<v Speaker 2>I'm going to preface this by saying that all of

0:31:40.720 --> 0:31:43.360
<v Speaker 2>the studies on the human microbiome, at least the ones

0:31:43.400 --> 0:31:46.560
<v Speaker 2>that I read in specific how it relates to sea diiff,

0:31:46.880 --> 0:31:50.600
<v Speaker 2>they're limited and have low sample sizes, So like, keep

0:31:50.640 --> 0:31:53.640
<v Speaker 2>that in mind. But there's still some really interesting things

0:31:53.920 --> 0:31:56.920
<v Speaker 2>from some review articles. So let me tell you what

0:31:57.000 --> 0:32:02.600
<v Speaker 2>I found studies that have low at people colonized with

0:32:02.720 --> 0:32:07.040
<v Speaker 2>sea diff versus not colonized with seed diff versus infected.

0:32:07.560 --> 0:32:12.120
<v Speaker 2>Have found that people who test positive and have symptoms

0:32:12.160 --> 0:32:16.080
<v Speaker 2>of infection with seed diff, so people sick from SEEDFF

0:32:16.160 --> 0:32:20.440
<v Speaker 2>with seed diff colitis have a significant reduction in their

0:32:20.560 --> 0:32:27.880
<v Speaker 2>overall microbial diversity and species richness. So for lots of

0:32:27.920 --> 0:32:30.000
<v Speaker 2>people who don't know, because I even had to regogle,

0:32:30.080 --> 0:32:34.520
<v Speaker 2>this species richness is just the actual number of different

0:32:34.520 --> 0:32:38.480
<v Speaker 2>bacterial species that are present, and diversity is a measure

0:32:38.560 --> 0:32:41.000
<v Speaker 2>of both that richness, so the number of species and

0:32:41.080 --> 0:32:45.000
<v Speaker 2>the abundance of these different species. So people who get

0:32:45.000 --> 0:32:49.480
<v Speaker 2>infected and get sick from seedediff have both low numbers

0:32:49.600 --> 0:32:54.080
<v Speaker 2>of bacterial species in their gut and low diversity of

0:32:54.120 --> 0:32:58.560
<v Speaker 2>those microbes. That's not surprising, right because we already said

0:32:58.600 --> 0:33:02.280
<v Speaker 2>these are generally people who might be sick or that

0:33:02.360 --> 0:33:07.160
<v Speaker 2>this is not a good competitor. But even people who

0:33:07.240 --> 0:33:11.200
<v Speaker 2>are colonized with cluster named diffy Stiel without any overt

0:33:11.200 --> 0:33:17.080
<v Speaker 2>signs of infection also have decreased species richness and diversity.

0:33:17.680 --> 0:33:22.640
<v Speaker 2>But the distribution of species is different in these two groups.

0:33:22.880 --> 0:33:25.840
<v Speaker 2>So it seems like there are certain species that are

0:33:25.920 --> 0:33:30.960
<v Speaker 2>more protective against infection, and you know what, it seems

0:33:31.080 --> 0:33:36.520
<v Speaker 2>like the effect of this microbiome composition on the amount

0:33:36.640 --> 0:33:40.040
<v Speaker 2>of bio acids that make it all the way to

0:33:40.200 --> 0:33:42.760
<v Speaker 2>your gut likely play a role.

0:33:43.400 --> 0:33:48.160
<v Speaker 3>Interesting Okay, Okay, So but I have questions about this,

0:33:48.440 --> 0:33:51.400
<v Speaker 3>uh huh. So this is what I think is difficult

0:33:51.440 --> 0:33:55.320
<v Speaker 3>a lot about microbiome research, right, is that there's still

0:33:55.360 --> 0:33:57.840
<v Speaker 3>so much we don't know, and so much is not

0:33:57.960 --> 0:34:02.239
<v Speaker 3>necessarily about the species identity, like the species role, so

0:34:02.280 --> 0:34:05.320
<v Speaker 3>like what's the functional role of those Like you might

0:34:05.360 --> 0:34:07.680
<v Speaker 3>have two different species, but they might play a similar

0:34:07.720 --> 0:34:08.719
<v Speaker 3>functional role.

0:34:08.760 --> 0:34:11.879
<v Speaker 2>Right, And so that's why they think that at least

0:34:11.920 --> 0:34:14.040
<v Speaker 2>they've been able to identify some of that in that

0:34:14.320 --> 0:34:17.040
<v Speaker 2>the functional role of some of these species might be

0:34:17.800 --> 0:34:22.120
<v Speaker 2>to decrease the amount of bio acids that activate seediff

0:34:22.200 --> 0:34:26.000
<v Speaker 2>spores and therefore allow seedediff colonization activation and colonization.

0:34:26.600 --> 0:34:29.360
<v Speaker 3>So then my second question is about the effect size.

0:34:29.440 --> 0:34:32.520
<v Speaker 3>So like what when you say reduce the amount of

0:34:32.560 --> 0:34:33.799
<v Speaker 3>bio like how much?

0:34:33.920 --> 0:34:34.560
<v Speaker 2>Good question?

0:34:34.640 --> 0:34:35.160
<v Speaker 4>I don't know.

0:34:35.600 --> 0:34:39.200
<v Speaker 2>Okay, yeah, yeah, it basically just shifts the ratio of

0:34:39.400 --> 0:34:42.560
<v Speaker 2>primary bile acids to secondary bio acids, but I don't

0:34:42.600 --> 0:34:43.840
<v Speaker 2>know by what numbers.

0:34:44.239 --> 0:34:48.680
<v Speaker 3>Okay, yeah, interesting, but it is really interesting.

0:34:49.880 --> 0:34:54.680
<v Speaker 2>Yeah, I agree, even though I agree, we really don't know.

0:34:54.840 --> 0:34:57.840
<v Speaker 4>And so it's also like, how do we then.

0:34:57.719 --> 0:35:01.120
<v Speaker 2>Translate that into something that can then you know, prevent infection.

0:35:01.360 --> 0:35:06.719
<v Speaker 2>It's still hard to do, right, Right, But what's important

0:35:06.840 --> 0:35:11.880
<v Speaker 2>is that the biggest risk factor for ceediff colitis is

0:35:12.080 --> 0:35:16.600
<v Speaker 2>antibiotic exposure, right. And it's not surprising when you look

0:35:16.719 --> 0:35:21.800
<v Speaker 2>at that studies that have looked at even very short

0:35:21.960 --> 0:35:27.680
<v Speaker 2>course exposure to antibiotics rapidly reduces the diversity of your

0:35:27.719 --> 0:35:31.880
<v Speaker 2>microbiome in your colon. And this diversity, this reduction in

0:35:31.960 --> 0:35:36.600
<v Speaker 2>diversity rather can persist for months and months, leaving you

0:35:36.640 --> 0:35:39.960
<v Speaker 2>potentially susceptible to something like an opportunistic pathogen.

0:35:40.640 --> 0:35:45.880
<v Speaker 3>Right, Because remember antibiotics are some are more targeted than others,

0:35:46.480 --> 0:35:48.839
<v Speaker 3>but none of them are like this will only kill

0:35:48.920 --> 0:35:55.200
<v Speaker 3>this species. It's there are going to be bystanders that

0:35:55.280 --> 0:35:59.160
<v Speaker 3>are wiped out just as a result of taking antibiotics.

0:35:58.480 --> 0:36:01.520
<v Speaker 2>Right, And any antibiotics that you take through your mouth

0:36:01.640 --> 0:36:03.680
<v Speaker 2>are going to make it to your gut, so they're

0:36:03.719 --> 0:36:05.359
<v Speaker 2>going to have some kind of an effect on your

0:36:05.400 --> 0:36:08.480
<v Speaker 2>gut microbiome, even if the antibiotics are for a kidney

0:36:08.480 --> 0:36:11.959
<v Speaker 2>infection or a skin infection, like it's going through your gut.

0:36:12.440 --> 0:36:12.720
<v Speaker 1>Yeah.

0:36:13.160 --> 0:36:14.719
<v Speaker 4>Yeah.

0:36:14.840 --> 0:36:17.720
<v Speaker 2>The other risk factors for infection, of course, are things

0:36:17.760 --> 0:36:22.120
<v Speaker 2>like exposure itself. And so the reason one of the

0:36:22.160 --> 0:36:27.040
<v Speaker 2>reasons that seadiff infection is so pervasive in healthcare environments

0:36:27.520 --> 0:36:31.520
<v Speaker 2>is because these spores exist in really really high concentrations

0:36:31.560 --> 0:36:35.000
<v Speaker 2>in the feces of people with sea diiff infection, which

0:36:35.040 --> 0:36:38.759
<v Speaker 2>means that they exist in really high concentrations at healthcare facilities,

0:36:39.040 --> 0:36:42.719
<v Speaker 2>and they're so environmentally resistant that they're really hard to

0:36:42.760 --> 0:36:45.960
<v Speaker 2>get rid of, and so they're really easily transmitted throughout

0:36:46.000 --> 0:36:47.760
<v Speaker 2>healthcare systems.

0:36:47.360 --> 0:36:52.160
<v Speaker 3>It's like a nightmare. It's yeah, that's how my grandmother

0:36:52.200 --> 0:36:56.040
<v Speaker 3>got sick from SEEDFF after having a knee replacement, and

0:36:56.080 --> 0:37:00.000
<v Speaker 3>it was it was horrible. I mean, it was absolutely

0:37:01.320 --> 0:37:02.440
<v Speaker 3>It's just horrific.

0:37:02.520 --> 0:37:02.719
<v Speaker 6>Yeah.

0:37:02.800 --> 0:37:03.800
<v Speaker 4>Yeah. Yeah.

0:37:04.440 --> 0:37:07.040
<v Speaker 2>Older age is also a really big risk factor.

0:37:07.560 --> 0:37:07.920
<v Speaker 3>Yeah.

0:37:07.960 --> 0:37:12.719
<v Speaker 2>So yeah, but it's not just healthcare. This just is

0:37:12.760 --> 0:37:17.080
<v Speaker 2>getting more and more depressing because there are some studies

0:37:17.160 --> 0:37:19.960
<v Speaker 2>that suggest that like thirty percent of people who end

0:37:20.040 --> 0:37:23.120
<v Speaker 2>up with a sea diff infection don't actually have any

0:37:23.200 --> 0:37:26.400
<v Speaker 2>risk factors, which also means that this isn't a problem

0:37:26.560 --> 0:37:30.440
<v Speaker 2>only in hospitals or care facilities. This is also something

0:37:30.440 --> 0:37:35.359
<v Speaker 2>that exists in the environment at large. So, and there

0:37:35.400 --> 0:37:38.799
<v Speaker 2>are some studies in Europe, in places like the Netherlands

0:37:38.800 --> 0:37:41.840
<v Speaker 2>that suggest that this what they're what they call community

0:37:41.880 --> 0:37:46.000
<v Speaker 2>acquired sea diff aka not from a hospital, actually has

0:37:46.040 --> 0:37:49.319
<v Speaker 2>a higher incidence than other causes of diarrhea that we

0:37:49.400 --> 0:37:51.799
<v Speaker 2>think of that we might think are more common, like

0:37:51.920 --> 0:37:55.879
<v Speaker 2>Camplobacter or sale manila. So it's a really important cause

0:37:55.920 --> 0:37:59.520
<v Speaker 2>of diarrhea that not only can be fatal but also

0:38:00.360 --> 0:38:05.400
<v Speaker 2>often causes recurrent infection. Yeah, so like ten to twenty

0:38:05.440 --> 0:38:08.040
<v Speaker 2>five percent of people will get at least one recurrent

0:38:08.080 --> 0:38:12.000
<v Speaker 2>infection after an initial infection, and of those people who

0:38:12.040 --> 0:38:15.720
<v Speaker 2>get it twice, something like forty to sixty five percent

0:38:15.760 --> 0:38:18.799
<v Speaker 2>of them may go on to have another and another.

0:38:19.640 --> 0:38:20.360
<v Speaker 3>Just like MRSA.

0:38:20.440 --> 0:38:24.320
<v Speaker 4>Again, yeah, exactly right. I think with c DIFF.

0:38:24.719 --> 0:38:27.359
<v Speaker 2>It's one of those infections that it has become so

0:38:27.960 --> 0:38:33.279
<v Speaker 2>clear how important the gut microbiome is to the establishment

0:38:33.360 --> 0:38:37.120
<v Speaker 2>and persistence of an infection like this, or to the

0:38:37.280 --> 0:38:41.640
<v Speaker 2>establishment and the susceptibility to an infection like this is.

0:38:42.880 --> 0:38:46.080
<v Speaker 3>Yeah, it's it's kind of like the perfect example of like,

0:38:46.920 --> 0:38:49.560
<v Speaker 3>oh hey, this thing that we didn't really think all

0:38:49.600 --> 0:38:53.480
<v Speaker 3>that much about turns out that there's a very important

0:38:53.520 --> 0:38:58.880
<v Speaker 3>balance and delicate balance, and the disruption of that is deadly.

0:38:59.480 --> 0:38:59.719
<v Speaker 4>Yeah.

0:39:00.080 --> 0:39:00.920
<v Speaker 2>Yeah, or it can be.

0:39:01.320 --> 0:39:08.120
<v Speaker 5>Yeah, that's all for the biology are I mean, it

0:39:08.200 --> 0:39:11.959
<v Speaker 5>is still a treatable infection a lot of the time,

0:39:12.239 --> 0:39:13.719
<v Speaker 5>but again because.

0:39:13.440 --> 0:39:19.080
<v Speaker 2>Of the recurrence and the resistance and the resistance. Well,

0:39:19.600 --> 0:39:21.640
<v Speaker 2>the good news is that later in.

0:39:21.560 --> 0:39:24.359
<v Speaker 4>This episode we are going to get to talk about.

0:39:26.160 --> 0:39:33.239
<v Speaker 2>Fecal transplants mm hmmm, fecal microbiota transplants a ka f MT,

0:39:33.960 --> 0:39:37.759
<v Speaker 2>putting healthy bacteria back into your colon. We'll talk more

0:39:37.800 --> 0:39:41.319
<v Speaker 2>about it later, as well as other novel treatments and

0:39:41.360 --> 0:39:47.319
<v Speaker 2>prevention strategies. But first, Aaron, tell me what's up with this?

0:39:47.440 --> 0:39:49.319
<v Speaker 2>Where did it come from? Has it always been with us?

0:39:49.360 --> 0:39:50.719
<v Speaker 2>Why is it making us so sick?

0:39:51.120 --> 0:39:55.399
<v Speaker 3>Good questions? Good questions. I will try to answer them

0:39:55.560 --> 0:40:33.239
<v Speaker 3>right after this break. The story that I want to

0:40:33.239 --> 0:40:37.120
<v Speaker 3>tell for this history section is really more like two stories,

0:40:37.760 --> 0:40:42.319
<v Speaker 3>each with a central main character to kind of origin stories,

0:40:42.440 --> 0:40:46.000
<v Speaker 3>to rise of the villain or hero stories, and then

0:40:46.080 --> 0:40:48.799
<v Speaker 3>only closer to the end, the two threads of the

0:40:48.880 --> 0:40:54.480
<v Speaker 3>stories meet, and unlike most straightforward hero versus villain or

0:40:54.520 --> 0:40:58.319
<v Speaker 3>good versus evil stories, the conflict doesn't drag on and on,

0:40:58.640 --> 0:41:02.520
<v Speaker 3>although there's still a material for many sequels, but rather

0:41:02.760 --> 0:41:06.319
<v Speaker 3>it resolves itself, I think, fairly quickly and in a

0:41:06.360 --> 0:41:11.800
<v Speaker 3>satisfying way. So who are these two main characters? Tell me, Well,

0:41:11.840 --> 0:41:14.680
<v Speaker 3>the first is probably fairly obvious because it's the topic

0:41:14.760 --> 0:41:19.120
<v Speaker 3>of today's episode, and you've already gone in great detail

0:41:19.160 --> 0:41:23.799
<v Speaker 3>about the biology of it, okay, Clostridium difficile. And the

0:41:23.840 --> 0:41:27.080
<v Speaker 3>second might be pretty obvious to since we've also already

0:41:27.080 --> 0:41:29.359
<v Speaker 3>talked about it. But I wanted to talk a bit

0:41:29.400 --> 0:41:34.279
<v Speaker 3>about the history of fecal microbiotic transplantations or FMT, which

0:41:34.320 --> 0:41:38.000
<v Speaker 3>are I think at least one of the obvious heroes

0:41:38.160 --> 0:41:42.000
<v Speaker 3>in this story. And I also fully acknowledge that it's

0:41:42.480 --> 0:41:46.560
<v Speaker 3>unfair and you know, anthropomorphizing to cast Seediff in the

0:41:46.680 --> 0:41:50.480
<v Speaker 3>villain role, and that you know, these bacteria might be

0:41:50.520 --> 0:41:54.800
<v Speaker 3>more accurately described as pawns without motive verguile, allowed only

0:41:54.840 --> 0:41:58.200
<v Speaker 3>to cause the damage they do because of a human

0:41:58.280 --> 0:42:03.040
<v Speaker 3>invention antibiotics. But I'm getting ahead of myself. And also

0:42:03.200 --> 0:42:05.200
<v Speaker 3>I don't know how much time we need to spend

0:42:05.239 --> 0:42:08.840
<v Speaker 3>in this particular episode about like anthropomorphizing of microbes and

0:42:08.880 --> 0:42:12.280
<v Speaker 3>the symbolic language that we use, like battle and war

0:42:12.440 --> 0:42:15.680
<v Speaker 3>on microbes whatever. It would be an interesting I would

0:42:15.680 --> 0:42:17.000
<v Speaker 3>like to write a paper about that.

0:42:17.000 --> 0:42:18.120
<v Speaker 4>That would be really interesting.

0:42:18.320 --> 0:42:23.759
<v Speaker 3>Yeah, what words do we use? Because words matter? Anyway, Seediff,

0:42:24.360 --> 0:42:28.520
<v Speaker 3>where did it come from? Well, the group Claustridium itself

0:42:28.680 --> 0:42:32.680
<v Speaker 3>is incredibly ancient. It's estimated to have diverged from the

0:42:32.719 --> 0:42:36.440
<v Speaker 3>bacterial domain about two point three four billion years ago,

0:42:36.640 --> 0:42:38.759
<v Speaker 3>which is what I saw, and that's right around the

0:42:38.800 --> 0:42:41.920
<v Speaker 3>same time that the atmosphere began to contain more and

0:42:42.000 --> 0:42:46.360
<v Speaker 3>more oxygen. And while I don't know the exact specific

0:42:46.480 --> 0:42:50.799
<v Speaker 3>origin of seaediff itself, I would imagine that based on

0:42:51.080 --> 0:42:54.480
<v Speaker 3>its genome and its ability to coexist with humans and

0:42:54.520 --> 0:42:57.160
<v Speaker 3>many other animals, it's been a part of our gut

0:42:57.160 --> 0:43:01.200
<v Speaker 3>microbiota and the microbiota of many other animals for quite

0:43:01.239 --> 0:43:06.000
<v Speaker 3>some time. And genomic analyzes of seediff also support this.

0:43:07.040 --> 0:43:09.919
<v Speaker 3>The genome of a particular strain of seedff, I think

0:43:09.960 --> 0:43:13.120
<v Speaker 3>one of the most predominant ones was fully sequenced and

0:43:13.160 --> 0:43:18.359
<v Speaker 3>annotated around two thousand and six, and this analysis is

0:43:18.360 --> 0:43:21.959
<v Speaker 3>a genomic look told us a lot about the ecology

0:43:22.040 --> 0:43:25.000
<v Speaker 3>of this bacterium and the type of relationship that it

0:43:25.040 --> 0:43:28.919
<v Speaker 3>has with its host like humans. So first, it told

0:43:28.960 --> 0:43:32.960
<v Speaker 3>us that sea diiff is really well adapted to coexist

0:43:33.080 --> 0:43:37.200
<v Speaker 3>with its host, not just to kill or pathogenically infect

0:43:37.239 --> 0:43:41.400
<v Speaker 3>and cause disease, which is in contrast to a relative

0:43:41.520 --> 0:43:46.040
<v Speaker 3>of seed Iff that we've talked about before, Claustridie and Bochelinum.

0:43:46.520 --> 0:43:51.080
<v Speaker 3>So Clustridi and Bochulinum in contrast, contains many unique genes

0:43:51.080 --> 0:43:55.520
<v Speaker 3>that are involved with like direct disease mortality, which is

0:43:55.600 --> 0:43:58.040
<v Speaker 3>just I think that's interesting because that does speak to

0:43:58.800 --> 0:44:04.440
<v Speaker 3>sort of the more multifaceted relationship that seediff has to humans.

0:44:04.640 --> 0:44:08.120
<v Speaker 3>It's not necessarily just a pathogen.

0:44:07.960 --> 0:44:11.759
<v Speaker 2>Right, So yeah, and it's and I mean it's not

0:44:12.239 --> 0:44:15.560
<v Speaker 2>just a path right, So it's.

0:44:14.719 --> 0:44:18.160
<v Speaker 3>A little bit it's a little bit deeper than that. Secondly,

0:44:18.440 --> 0:44:20.960
<v Speaker 3>and one of the things that I find super interesting

0:44:21.520 --> 0:44:24.640
<v Speaker 3>is that the species itself, like you know, all the

0:44:24.680 --> 0:44:27.279
<v Speaker 3>isolates and strains and whatever that make up seed iff

0:44:27.320 --> 0:44:31.600
<v Speaker 3>that we know about, they are incredibly diverse, even when

0:44:31.600 --> 0:44:36.120
<v Speaker 3>compared to other bacterial species that have high genetic variability. So,

0:44:36.160 --> 0:44:39.080
<v Speaker 3>according to one paper I read by night at All

0:44:39.120 --> 0:44:43.200
<v Speaker 3>from twenty fifteen, the amount of shared core genome of

0:44:43.239 --> 0:44:47.400
<v Speaker 3>seed iff, So in my understanding, that's the amount of

0:44:47.440 --> 0:44:50.200
<v Speaker 3>genome shared across all isolates of seed iff, like the

0:44:50.200 --> 0:44:53.480
<v Speaker 3>core genome or whatever is as low as sixteen percent,

0:44:54.600 --> 0:44:58.759
<v Speaker 3>what which is lower than has been observed for any

0:44:58.760 --> 0:45:03.920
<v Speaker 3>other bacterial species so far. And so what does that mean? Well, so,

0:45:04.040 --> 0:45:07.480
<v Speaker 3>of course there's like natural genomic variation across members of

0:45:07.520 --> 0:45:10.279
<v Speaker 3>an individual species like aaron, you and I, we don't

0:45:10.320 --> 0:45:14.680
<v Speaker 3>share the same exact genome, right, But what this means

0:45:14.880 --> 0:45:18.480
<v Speaker 3>is essentially that the amount of genomic variation across sea

0:45:18.520 --> 0:45:21.239
<v Speaker 3>diiff is more along what you might expect for like

0:45:21.480 --> 0:45:25.800
<v Speaker 3>members of a different genus, rather than among strains within

0:45:25.880 --> 0:45:30.680
<v Speaker 3>a species. And so this research and other research has

0:45:30.760 --> 0:45:36.080
<v Speaker 3>called into question Seaediff's designation as one species, with more

0:45:36.160 --> 0:45:39.200
<v Speaker 3>researchers suggesting that we take a new approach to the

0:45:39.239 --> 0:45:43.799
<v Speaker 3>taxonomy of seediff, so for instance, by recognizing certain strains

0:45:43.840 --> 0:45:47.920
<v Speaker 3>as subspecies or separate species entirely, like the.

0:45:48.080 --> 0:45:50.279
<v Speaker 4>Non toxogenic versus toxogenic that.

0:45:50.320 --> 0:45:54.480
<v Speaker 3>Kind of something like that yeah, and so what does

0:45:54.520 --> 0:45:58.319
<v Speaker 3>that mean in practice, I don't know, but I think

0:45:58.360 --> 0:46:01.000
<v Speaker 3>it could have a lot to do, like, I don't

0:46:01.040 --> 0:46:03.560
<v Speaker 3>know the evolution of this, trying to predict the evolution

0:46:03.680 --> 0:46:07.800
<v Speaker 3>and the geographic spread, which wants to worry about, I

0:46:07.840 --> 0:46:08.200
<v Speaker 3>don't know.

0:46:08.920 --> 0:46:10.000
<v Speaker 4>It's also about.

0:46:09.960 --> 0:46:12.600
<v Speaker 2>It would really change the way that we've gotten estimates

0:46:12.600 --> 0:46:16.160
<v Speaker 2>for things like seediff colonization in the past, because right

0:46:16.239 --> 0:46:18.920
<v Speaker 2>that it's been like all of these strains lumped together.

0:46:19.560 --> 0:46:22.440
<v Speaker 3>Hmm, yeah, so it would it would definitely change like

0:46:22.480 --> 0:46:24.560
<v Speaker 3>the disease burden or how we look at those numbers.

0:46:24.760 --> 0:46:25.680
<v Speaker 4>Yeah. Yeah.

0:46:25.760 --> 0:46:29.239
<v Speaker 3>So let's go back to when our villain, Seadiff was

0:46:29.280 --> 0:46:33.760
<v Speaker 3>first discovered, or as it was first named Bacillis dificillis.

0:46:34.840 --> 0:46:37.160
<v Speaker 3>And so, as you mentioned, Aaron, yes, this happened a

0:46:37.200 --> 0:46:40.759
<v Speaker 3>long time ago, back in nineteen thirty five. Specifically, the

0:46:40.840 --> 0:46:44.279
<v Speaker 3>name was changed to Claustridium difficile in nineteen thirty eight.

0:46:44.640 --> 0:46:47.880
<v Speaker 3>And it happened when these two researchers in Denver, which

0:46:47.960 --> 0:46:50.479
<v Speaker 3>I wanted to shout out because I don't think I've

0:46:50.520 --> 0:46:53.120
<v Speaker 3>told everybody here on the podcast, but I moved to

0:46:53.160 --> 0:46:56.080
<v Speaker 3>Denver this year and I love it. It's incredible, it's

0:46:56.080 --> 0:47:01.480
<v Speaker 3>the best. But these two researchers were named Elizabeth O'Toole,

0:47:02.040 --> 0:47:05.680
<v Speaker 3>and they collected the maconium and feces of ten newborn

0:47:05.719 --> 0:47:08.200
<v Speaker 3>infants at a hospital to see what microbes might be

0:47:08.239 --> 0:47:11.440
<v Speaker 3>in there. And I thought that was interesting because I

0:47:11.440 --> 0:47:15.360
<v Speaker 3>guess I didn't realize that the characterization of the microbiome,

0:47:15.760 --> 0:47:19.040
<v Speaker 3>or at least like the recognition of endosymbiotic bacteria, had

0:47:19.080 --> 0:47:23.160
<v Speaker 3>started so early. And it's true that a lot of

0:47:23.200 --> 0:47:26.000
<v Speaker 3>the early germ theory days were focused on like matching

0:47:26.080 --> 0:47:28.960
<v Speaker 3>a disease to a pathogen, like, oh, we found a bacterium,

0:47:29.080 --> 0:47:31.160
<v Speaker 3>it has to cause a disease, what does it cause?

0:47:31.960 --> 0:47:34.200
<v Speaker 3>So you know, based on that, when people were just

0:47:34.239 --> 0:47:37.040
<v Speaker 3>like hunting microbes, it does make sense that people would

0:47:37.040 --> 0:47:39.640
<v Speaker 3>have encountered some over and over again that were not

0:47:39.680 --> 0:47:45.839
<v Speaker 3>associated with any inherent or any apparent disease. But I

0:47:45.880 --> 0:47:48.480
<v Speaker 3>think they're also Around this time, there had been a

0:47:48.480 --> 0:47:52.880
<v Speaker 3>growing recognition that not all bacteria were bad, and that

0:47:53.040 --> 0:47:56.520
<v Speaker 3>some might be helpful or at the very least neutral,

0:47:57.040 --> 0:48:00.000
<v Speaker 3>And basically that's what it seems like Hall and Otool

0:48:00.200 --> 0:48:02.200
<v Speaker 3>had set out to do with this study, just like

0:48:02.360 --> 0:48:05.880
<v Speaker 3>find out what was there, and especially the way that

0:48:05.960 --> 0:48:10.320
<v Speaker 3>these microbe communities changed during the first ten days after birth.

0:48:10.840 --> 0:48:13.920
<v Speaker 3>And in their screening they found several species of bacteria

0:48:14.000 --> 0:48:17.240
<v Speaker 3>that had already been described, but they also found something

0:48:17.280 --> 0:48:21.120
<v Speaker 3>new in several of the samples. Quote an actively motile,

0:48:21.239 --> 0:48:25.120
<v Speaker 3>heavily bodied rod with elongate, subterminal or nearly terminal spores

0:48:25.160 --> 0:48:28.799
<v Speaker 3>of about the same diameter of the rods. Ooh man,

0:48:29.160 --> 0:48:35.040
<v Speaker 3>what riveting reading riveting is right? And they named this

0:48:35.160 --> 0:48:39.520
<v Speaker 3>new species Bacillis dificillis because of how difficult it was

0:48:39.600 --> 0:48:42.960
<v Speaker 3>to isolate and study under lab conditions. It's just like

0:48:43.040 --> 0:48:44.279
<v Speaker 3>a finicky guy.

0:48:44.640 --> 0:48:46.480
<v Speaker 4>Finicky. It's anaerobic, you.

0:48:46.440 --> 0:48:50.520
<v Speaker 3>Know, Yeah, they're finicky. Then, to see if they could

0:48:50.560 --> 0:48:53.319
<v Speaker 3>figure out more about the role of this bacterium, they

0:48:53.360 --> 0:48:56.920
<v Speaker 3>infected rabbits and guinea pigs with it to see what

0:48:56.920 --> 0:48:59.400
<v Speaker 3>would happen, and they were surprised to find that it

0:48:59.440 --> 0:49:03.040
<v Speaker 3>seemed white pathogenic to them, or at least that the

0:49:03.040 --> 0:49:06.120
<v Speaker 3>bacterium produced a toxin that could lead to death or

0:49:06.160 --> 0:49:11.520
<v Speaker 3>severe disease in these lab animals, although the toxins wouldn't

0:49:11.560 --> 0:49:15.279
<v Speaker 3>be described until nineteen seventy four, when Green at All

0:49:15.360 --> 0:49:18.080
<v Speaker 3>isolated it from the stools of guinea pigs treated with penicillin,

0:49:18.360 --> 0:49:20.240
<v Speaker 3>although even then it was thought to be a virus,

0:49:20.280 --> 0:49:22.600
<v Speaker 3>and that connection to seed iff wouldn't be made until later.

0:49:23.600 --> 0:49:25.840
<v Speaker 3>And that's all kind of like part of the theme

0:49:25.960 --> 0:49:29.640
<v Speaker 3>of seediff. It's like flying by under the radar, not

0:49:29.680 --> 0:49:33.759
<v Speaker 3>really acting suspicious or you know, earning any suspicion. That

0:49:33.840 --> 0:49:37.000
<v Speaker 3>kind of makes up a lot of the history of seediff.

0:49:38.239 --> 0:49:41.040
<v Speaker 3>And so this paper that I talked about, the Hollino

0:49:41.160 --> 0:49:44.080
<v Speaker 3>tool paper where seediff was first described, that came out

0:49:44.120 --> 0:49:47.960
<v Speaker 3>in nineteen thirty five, and between the years nineteen forty

0:49:48.160 --> 0:49:51.120
<v Speaker 3>and nineteen sixty two, there were only two mentions of

0:49:51.200 --> 0:49:55.400
<v Speaker 3>seadiff infections in humans in the medical literature, and in

0:49:55.440 --> 0:49:58.880
<v Speaker 3>both of these studies, seedediff was not suspected to be

0:49:58.920 --> 0:50:02.279
<v Speaker 3>pathogenic to humans, like, it wasn't written about as a

0:50:02.280 --> 0:50:06.400
<v Speaker 3>potential pathogen, and Hallan O'Toole did, like based on their

0:50:06.600 --> 0:50:09.480
<v Speaker 3>rabbit and giddapig studies, they did say, oh, maybe we

0:50:09.520 --> 0:50:11.759
<v Speaker 3>want to keep an eye out for this in infants

0:50:11.800 --> 0:50:16.080
<v Speaker 3>as a possibility of causing disease, but it didn't. There

0:50:16.080 --> 0:50:18.040
<v Speaker 3>didn't seem to be a whole lot of follow up

0:50:18.440 --> 0:50:20.600
<v Speaker 3>and there didn't really seem to need to be a

0:50:20.600 --> 0:50:24.680
<v Speaker 3>whole lot of follow up because it doesn't seem as though,

0:50:24.680 --> 0:50:26.440
<v Speaker 3>at least from what I can tell, that there was

0:50:26.480 --> 0:50:30.239
<v Speaker 3>a silent epidemic of sea diff during that time. So

0:50:30.400 --> 0:50:33.600
<v Speaker 3>like since Hallan o'tool described it to I don't know,

0:50:33.600 --> 0:50:38.120
<v Speaker 3>the nineteen fifties or something, and if anything, you know,

0:50:38.320 --> 0:50:42.600
<v Speaker 3>I think I'm all side with you in being surprised

0:50:42.640 --> 0:50:46.600
<v Speaker 3>at how early sea diiff was described, like nineteen thirty five.

0:50:46.719 --> 0:50:48.400
<v Speaker 3>At first, I was like, wow, that's so recent, and

0:50:48.400 --> 0:50:51.680
<v Speaker 3>then I was like, wait a second, Yeah, based on biology, No,

0:50:51.800 --> 0:50:55.600
<v Speaker 3>that's like very surprisingly early.

0:50:55.760 --> 0:51:00.960
<v Speaker 2>Right, especially because it was yeah, not causing disease, mhmm hmm.

0:51:01.160 --> 0:51:05.240
<v Speaker 3>Yeah. And I definitely didn't find anything or read anything

0:51:05.320 --> 0:51:09.960
<v Speaker 3>about historical infections of seediff or ancient writings describing the disease.

0:51:10.480 --> 0:51:13.160
<v Speaker 3>I mean, you know, of course, there's plenty to choose

0:51:13.160 --> 0:51:16.440
<v Speaker 3>from in terms of ancient writings of diarrhea. It's always

0:51:16.480 --> 0:51:19.799
<v Speaker 3>been a part of human existence, and I'm sure that

0:51:19.920 --> 0:51:24.280
<v Speaker 3>seadiff took on the role of pathogen occasionally in human history.

0:51:25.160 --> 0:51:29.480
<v Speaker 3>And the first description we have of pseudomembranous colitis, for example,

0:51:29.520 --> 0:51:34.160
<v Speaker 3>which is that horrible sounding condition caused by seediff is

0:51:34.239 --> 0:51:37.799
<v Speaker 3>from eighteen ninety three, reported in a twenty two year

0:51:37.840 --> 0:51:41.160
<v Speaker 3>old woman who had recently undergone surgery for a gastric tumor.

0:51:41.680 --> 0:51:46.520
<v Speaker 3>She later developed severe diarrhea and died. And so maybe

0:51:46.520 --> 0:51:49.360
<v Speaker 3>that was caused by sea diiff, but we have no

0:51:49.440 --> 0:51:53.640
<v Speaker 3>way of knowing for sure. But beyond you know, cases

0:51:53.719 --> 0:51:57.080
<v Speaker 3>like that, seedediff was probably just part of the background,

0:51:57.280 --> 0:52:00.240
<v Speaker 3>like minding its own business, popping up here and there,

0:52:00.680 --> 0:52:02.960
<v Speaker 3>and it likely would have stayed that way, just like

0:52:03.000 --> 0:52:08.520
<v Speaker 3>a wallflower on your gut gut flower. But humans intervened,

0:52:09.320 --> 0:52:14.120
<v Speaker 3>And of course I'm talking about the rise of antibiotics.

0:52:14.320 --> 0:52:17.400
<v Speaker 3>So the widespread use of antibiotics began in the nineteen

0:52:17.480 --> 0:52:21.960
<v Speaker 3>forties with penicillin, and it continued to grow and grow

0:52:22.080 --> 0:52:27.320
<v Speaker 3>as more antibiotics, such as vankomycin were discovered and then administered.

0:52:27.840 --> 0:52:32.359
<v Speaker 3>By the nineteen fifties, antibiotics were readily available everywhere and

0:52:32.480 --> 0:52:36.759
<v Speaker 3>frequently prescribed, and the ones most commonly reached for were

0:52:36.920 --> 0:52:40.239
<v Speaker 3>broad spectrum antibiotics, the ones that would wipe out not

0:52:40.280 --> 0:52:42.680
<v Speaker 3>only whatever was making you sick, but a bunch of

0:52:42.680 --> 0:52:46.239
<v Speaker 3>other species right along with it. Casualties of the War

0:52:46.280 --> 0:52:49.960
<v Speaker 3>on Bacteria, and also like it's still reasonable to prescribe

0:52:50.000 --> 0:52:53.120
<v Speaker 3>broad spectrum antibiotics, especially when you're someone sick and you

0:52:53.160 --> 0:52:55.280
<v Speaker 3>don't know what it is and you need to try something.

0:52:55.520 --> 0:52:59.239
<v Speaker 2>Yeah, it's still very important that they exist. And I'm

0:52:59.239 --> 0:53:04.200
<v Speaker 2>not I am so yeah, yeah, we are still pro antibiotic, right.

0:53:04.480 --> 0:53:07.200
<v Speaker 3>This isn't like antibiotics are not the are not part

0:53:07.239 --> 0:53:10.359
<v Speaker 3>of the villain. They're they're just yeah.

0:53:09.840 --> 0:53:11.520
<v Speaker 4>They're just a supporting character.

0:53:12.239 --> 0:53:15.720
<v Speaker 3>Yeah, but this is an inevitable consequence.

0:53:16.040 --> 0:53:19.640
<v Speaker 2>We are pro good antibiotics stewardship, Aaron.

0:53:19.840 --> 0:53:23.759
<v Speaker 3>That is what we are pro. That's a very very

0:53:23.840 --> 0:53:29.720
<v Speaker 3>important caveat there. Yeah. Okay, So shortly after the rise

0:53:29.800 --> 0:53:34.040
<v Speaker 3>of antibiotics in the nineteen fifties and nineteen sixties, doctors

0:53:34.080 --> 0:53:38.879
<v Speaker 3>began to notice a rise in pseudo membranous colitis, and

0:53:39.200 --> 0:53:42.160
<v Speaker 3>a rise that seemed to be tied to antibiotic use.

0:53:43.000 --> 0:53:46.080
<v Speaker 3>Surgeons had observed rates as high as fourteen to twenty

0:53:46.120 --> 0:53:49.960
<v Speaker 3>seven percent among people who had recently undergone surgery.

0:53:50.360 --> 0:53:52.080
<v Speaker 4>Which is high, that's very high.

0:53:52.400 --> 0:53:55.840
<v Speaker 3>Yeah, And of course the prescription of antibiotics after surgery

0:53:56.480 --> 0:53:59.520
<v Speaker 3>was and continues to be a very common practice and

0:53:59.560 --> 0:54:03.600
<v Speaker 3>it's import and to prevent secondary infections. But even when

0:54:03.640 --> 0:54:09.400
<v Speaker 3>people started to recognize the link between pseudomembranius colitis and antibiotics,

0:54:09.520 --> 0:54:12.640
<v Speaker 3>ceedif wasn't really on the short or even long list

0:54:12.719 --> 0:54:16.920
<v Speaker 3>of suspects. Most people actually thought that staph aureus was

0:54:17.040 --> 0:54:20.560
<v Speaker 3>the likely culprit since it was often isolated from the

0:54:20.560 --> 0:54:25.439
<v Speaker 3>patient's stool. And because of this, vancomycin, which was used

0:54:25.440 --> 0:54:27.840
<v Speaker 3>to kill the staff, began to be given as the

0:54:27.840 --> 0:54:32.000
<v Speaker 3>standard treatment for pseudomembranus colitis starting in the late nineteen fifties,

0:54:33.320 --> 0:54:37.200
<v Speaker 3>but over the next couple of decades, staph orias seemed

0:54:37.320 --> 0:54:39.880
<v Speaker 3>less and less likely to be the cause since it

0:54:39.960 --> 0:54:43.280
<v Speaker 3>wasn't really reliably found in the stool of many people

0:54:43.360 --> 0:54:48.399
<v Speaker 3>with pseudomembranus colitis, and the disease itself, like the rates

0:54:48.400 --> 0:54:52.960
<v Speaker 3>of the disease didn't really seem to go down at all.

0:54:53.120 --> 0:54:56.960
<v Speaker 3>A study in the nineteen seventies firmly displaced staph areas

0:54:57.040 --> 0:55:01.719
<v Speaker 3>as the causative agent, and through suspicion on antibiotics themselves

0:55:03.120 --> 0:55:04.960
<v Speaker 3>because they were like, well, if it's not staff, what

0:55:05.040 --> 0:55:09.160
<v Speaker 3>the heck is it? And this study followed two hundred

0:55:09.160 --> 0:55:13.200
<v Speaker 3>patients at a hospital who had been given clindamycin. Twenty

0:55:13.239 --> 0:55:18.200
<v Speaker 3>one percent developed diarrhea and ten percent developed pseudomembranus colitis,

0:55:19.040 --> 0:55:23.960
<v Speaker 3>but stool cultures were all negative for staphorus. And so

0:55:24.000 --> 0:55:27.440
<v Speaker 3>it was this study and another study from New Zealand

0:55:27.800 --> 0:55:31.799
<v Speaker 3>that linked diarrhea and colitis with antibiotics that kind of

0:55:31.960 --> 0:55:36.000
<v Speaker 3>caught the wider attention of the medical community, including a

0:55:36.200 --> 0:55:40.319
<v Speaker 3>doctor John G. Bartlett, who was then at Tufts University.

0:55:41.239 --> 0:55:45.840
<v Speaker 3>So he had begun investigating antibiotic induced diarrhea and pseudomembranus

0:55:45.840 --> 0:55:50.400
<v Speaker 3>colitis in the mid nineteen seventies, and in nineteen seventy

0:55:50.440 --> 0:55:53.719
<v Speaker 3>eight he and his team published a series of papers

0:55:53.840 --> 0:55:59.240
<v Speaker 3>in which they finally revealed the link between a toxin

0:55:59.320 --> 0:56:04.200
<v Speaker 3>producing class stridium and pseudomembranus colitis. And then he followed

0:56:04.239 --> 0:56:08.239
<v Speaker 3>up this research by showing that he had found seediff

0:56:08.440 --> 0:56:11.520
<v Speaker 3>in the stool samples of several of the individuals in

0:56:11.560 --> 0:56:14.319
<v Speaker 3>that first study of two hundred patients that they could

0:56:14.360 --> 0:56:16.600
<v Speaker 3>find no staff, they were like, well, we don't know

0:56:16.640 --> 0:56:18.680
<v Speaker 3>what it is. And so he actually got some of

0:56:18.680 --> 0:56:22.920
<v Speaker 3>those samples and was like, seadiffs here as well, so

0:56:22.960 --> 0:56:26.000
<v Speaker 3>that kind of was just like boom. This clearly made

0:56:26.080 --> 0:56:31.040
<v Speaker 3>the link, and he went on to uncover a great

0:56:31.080 --> 0:56:34.719
<v Speaker 3>deal more about seediff, which also hugely opened up the

0:56:34.760 --> 0:56:38.800
<v Speaker 3>field for other researchers to characterize its toxins, to examine

0:56:38.840 --> 0:56:43.840
<v Speaker 3>strain diversity, and to understand transmission dynamics. Like from the

0:56:43.920 --> 0:56:48.960
<v Speaker 3>late nineteen seventies to now, we know an incredible amount

0:56:49.400 --> 0:56:53.960
<v Speaker 3>about this bacterium. It's pretty amazing, I mean, and that

0:56:54.000 --> 0:56:57.000
<v Speaker 3>also speaks to the huge public health impact that it has.

0:56:58.239 --> 0:57:02.360
<v Speaker 3>With these late nineteen seventies studies from Bartlett and his group,

0:57:02.560 --> 0:57:05.319
<v Speaker 3>the field of sea diiff was blown wide open. It

0:57:05.400 --> 0:57:08.120
<v Speaker 3>seemed that once researchers started looking for the pathogen, they

0:57:08.120 --> 0:57:13.200
<v Speaker 3>found it everywhere, and in increasingly high numbers. The continued

0:57:13.320 --> 0:57:18.440
<v Speaker 3>use of antibiotics, especially cephalosporins, which seadiff is intrinsically resistant to,

0:57:19.240 --> 0:57:22.160
<v Speaker 3>during the nineteen eighties and nineteen nineties it led to

0:57:22.200 --> 0:57:26.400
<v Speaker 3>a huge rise in seaediff overall, which of course led

0:57:26.400 --> 0:57:30.360
<v Speaker 3>to a huge increase in the diversity of strains, including

0:57:30.400 --> 0:57:35.080
<v Speaker 3>the emergence of highly virulent strains, and over time, the

0:57:35.200 --> 0:57:39.880
<v Speaker 3>characterization of seediff as a hospital acquired pathogen and one

0:57:39.880 --> 0:57:41.520
<v Speaker 3>that you have nothing to worry about if you aren't

0:57:41.560 --> 0:57:43.000
<v Speaker 3>in a hospital, or if you don't work in a

0:57:43.000 --> 0:57:46.520
<v Speaker 3>hospital setting, or if you aren't taking antibiotics, like you said, Aaron,

0:57:46.560 --> 0:57:51.439
<v Speaker 3>that's become increasingly less accurate. Community acquired infections have become

0:57:51.480 --> 0:57:56.440
<v Speaker 3>more common, as I read have animal associated infections, either

0:57:56.480 --> 0:58:00.240
<v Speaker 3>through direct contact as well as potentially food borne, which

0:58:00.240 --> 0:58:03.080
<v Speaker 3>has led to many people calling for a one health

0:58:03.080 --> 0:58:08.120
<v Speaker 3>approach for this pathogen. Oh, I know, one health always well.

0:58:08.080 --> 0:58:10.840
<v Speaker 2>Yeah, but this, like the numbers that I saw on

0:58:11.000 --> 0:58:16.080
<v Speaker 2>like ground meats being contaminated, was terrifying.

0:58:16.480 --> 0:58:17.640
<v Speaker 3>Are you going to share them?

0:58:17.960 --> 0:58:18.160
<v Speaker 1>Oh?

0:58:18.280 --> 0:58:20.320
<v Speaker 2>I didn't write them down, but I should pull them

0:58:20.360 --> 0:58:22.160
<v Speaker 2>back up because it is awful.

0:58:22.400 --> 0:58:22.720
<v Speaker 1>Okay.

0:58:24.240 --> 0:58:27.880
<v Speaker 3>Yeah. Because also the other thing, and we touched on

0:58:27.920 --> 0:58:30.920
<v Speaker 3>this in I think our antibiotics episode, we had to

0:58:30.960 --> 0:58:35.160
<v Speaker 3>have maybe the second one. The overuse of antibiotics in

0:58:35.400 --> 0:58:40.040
<v Speaker 3>both livestock and like other animals has led to increasingly

0:58:40.160 --> 0:58:44.640
<v Speaker 3>resistant and difficult to treat strains of sea diff Sea

0:58:44.680 --> 0:58:51.440
<v Speaker 3>diiff is now like quite expectedly an enormous global problem,

0:58:51.880 --> 0:58:53.919
<v Speaker 3>which I know you'll get into more later.

0:58:54.560 --> 0:58:54.760
<v Speaker 4>Yeah.

0:58:54.960 --> 0:58:59.120
<v Speaker 3>It had this dramatic rise from zero to villain that

0:58:59.240 --> 0:59:03.800
<v Speaker 3>was made possible only buy antibiotics. So maybe it's time

0:59:03.920 --> 0:59:08.120
<v Speaker 3>we looked for and out of the box solution or

0:59:08.160 --> 0:59:09.320
<v Speaker 3>out of the bowl solution.

0:59:09.920 --> 0:59:18.720
<v Speaker 2>I don't know, no, no, okay, Oh goodness.

0:59:18.960 --> 0:59:21.880
<v Speaker 3>So you know the saying like fight fire with fire?

0:59:22.600 --> 0:59:24.240
<v Speaker 4>Oh sure, what about.

0:59:24.000 --> 0:59:25.360
<v Speaker 3>Fighting poop with poop?

0:59:25.680 --> 0:59:26.360
<v Speaker 4>Oh? Aaron?

0:59:30.160 --> 0:59:32.160
<v Speaker 3>You know I can't resist to come on, I love it.

0:59:32.200 --> 0:59:39.440
<v Speaker 3>I do introducing fecal microbiota transplants. So at the end

0:59:39.480 --> 0:59:41.600
<v Speaker 3>of this episode you'll get to hear a whole lot

0:59:41.680 --> 0:59:45.280
<v Speaker 3>more about the how and the why of fecal microbiotic transplants,

0:59:45.280 --> 0:59:47.880
<v Speaker 3>and I can't wait to get into it, but I

0:59:47.960 --> 0:59:50.600
<v Speaker 3>wanted to first provide a bit of context, a bit

0:59:50.640 --> 0:59:52.640
<v Speaker 3>of the where did this come from? And how did

0:59:52.680 --> 0:59:56.240
<v Speaker 3>we get to where we are today type of thing. Essentially,

0:59:56.520 --> 0:59:59.720
<v Speaker 3>like you said, Aaron, the idea behind fecal microbiota transplants

0:59:59.760 --> 1:00:02.800
<v Speaker 3>is that you take the fecal material from a healthy

1:00:02.840 --> 1:00:05.760
<v Speaker 3>donor and put it in the intestinal tract of someone

1:00:05.840 --> 1:00:09.040
<v Speaker 3>who has some sort of GI disorder, often because their

1:00:09.240 --> 1:00:13.720
<v Speaker 3>microbiota is disrupted, and you do this in order to

1:00:13.880 --> 1:00:17.680
<v Speaker 3>change the gut microbiota, the composition of the microbes in

1:00:17.760 --> 1:00:21.000
<v Speaker 3>the gut with the hope that this infusion acts like

1:00:21.040 --> 1:00:24.440
<v Speaker 3>a hard reset and can take out the disease, kind

1:00:24.440 --> 1:00:25.360
<v Speaker 3>of get things.

1:00:25.080 --> 1:00:27.560
<v Speaker 2>Back to normal, like unplug it and pluck it back

1:00:27.560 --> 1:00:27.960
<v Speaker 2>in again.

1:00:28.120 --> 1:00:33.200
<v Speaker 3>Exactly, And it works in many cases, like remarkably. Well,

1:00:33.840 --> 1:00:38.040
<v Speaker 3>it's beautiful, Like it's a beautiful thing. I love it.

1:00:38.160 --> 1:00:41.360
<v Speaker 3>I get chills when I think about FMT's They're just

1:00:42.960 --> 1:00:44.600
<v Speaker 3>so satisfyingly wonderful.

1:00:44.920 --> 1:00:46.000
<v Speaker 4>It's so elegant.

1:00:46.480 --> 1:00:48.200
<v Speaker 3>Yeah, it is.

1:00:48.240 --> 1:00:50.760
<v Speaker 2>It's weird to say because it's poop, but it is.

1:00:51.080 --> 1:00:53.600
<v Speaker 3>I think it's it's the simplicity of it and the

1:00:53.600 --> 1:00:56.400
<v Speaker 3>logic of it is so of course.

1:00:57.040 --> 1:00:57.800
<v Speaker 4>Yeah.

1:00:58.160 --> 1:01:01.200
<v Speaker 3>Yeah, So who first came up with this idea that

1:01:01.240 --> 1:01:03.920
<v Speaker 3>healthy poop could cure someone's bad poop?

1:01:04.360 --> 1:01:05.360
<v Speaker 4>Yeah, I don't know. Tell me.

1:01:06.080 --> 1:01:10.040
<v Speaker 3>It actually goes way way back, all the way back

1:01:10.240 --> 1:01:12.560
<v Speaker 3>to the fourth century in China.

1:01:12.920 --> 1:01:13.360
<v Speaker 1>CE.

1:01:13.720 --> 1:01:15.240
<v Speaker 3>Yeah, fourth century CE.

1:01:15.440 --> 1:01:19.480
<v Speaker 2>I love that erin And it is somehow shocking and

1:01:19.600 --> 1:01:23.040
<v Speaker 2>also not surprising at all if you've ever listened to

1:01:23.120 --> 1:01:24.320
<v Speaker 2>this podcast, I feel.

1:01:24.080 --> 1:01:26.280
<v Speaker 3>Like exactly, yeah.

1:01:26.600 --> 1:01:26.840
<v Speaker 4>Yeah.

1:01:26.880 --> 1:01:30.400
<v Speaker 3>So it was described in the first Chinese Handbook of

1:01:30.440 --> 1:01:34.440
<v Speaker 3>Emergency Medicine, and in this book it was recommended that

1:01:34.480 --> 1:01:38.400
<v Speaker 3>if you had food poisoning or severe diarrhea. You should

1:01:39.120 --> 1:01:44.320
<v Speaker 3>ingest fecal suspension by mouth. Wow mm hmmm. And it

1:01:44.400 --> 1:01:48.240
<v Speaker 3>was described as not just being like somewhat successful, like oh,

1:01:48.400 --> 1:01:52.200
<v Speaker 3>try this and it might work, but like miraculous bringing

1:01:52.280 --> 1:01:56.120
<v Speaker 3>back patients from the brink of death. And this isn't

1:01:56.160 --> 1:01:59.120
<v Speaker 3>the only reference to early fecal transplants either. In the

1:01:59.200 --> 1:02:03.720
<v Speaker 3>traditional Chinese medicine book Compendium of Materia Medica, a series

1:02:03.760 --> 1:02:07.760
<v Speaker 3>of prescriptions are described that are essentially various preparations of

1:02:07.880 --> 1:02:12.400
<v Speaker 3>human fecal material. I've got your fermented fecal solution, fresh

1:02:12.400 --> 1:02:16.880
<v Speaker 3>fecal suspension, dry feces, infant feces, take your pick all

1:02:16.960 --> 1:02:22.400
<v Speaker 3>for the effective treatment of abdominal diseases with severe diarrhea, fever, pain, vomiting,

1:02:22.520 --> 1:02:27.800
<v Speaker 3>and constipation, just various things. And so reading about this

1:02:28.160 --> 1:02:31.040
<v Speaker 3>got me thinking about all of the times that we

1:02:31.160 --> 1:02:35.680
<v Speaker 3>have laughed and laughed and laughed about ancient or medieval

1:02:35.720 --> 1:02:38.200
<v Speaker 3>cures and how ridiculous they are.

1:02:39.040 --> 1:02:40.200
<v Speaker 4>I know, I know.

1:02:40.440 --> 1:02:43.040
<v Speaker 3>And it struck me that if we had done this podcast,

1:02:43.080 --> 1:02:46.320
<v Speaker 3>this episode twenty or thirty years ago, we may have

1:02:46.440 --> 1:02:51.560
<v Speaker 3>similarly laughed at yellow soup, at actually eating poop. But

1:02:51.640 --> 1:02:56.520
<v Speaker 3>we're not laughing now, except that ourselves. Maybe that's Yeah,

1:02:56.520 --> 1:03:00.160
<v Speaker 3>that's hard, Aaron, I know, and that's not to say,

1:03:00.400 --> 1:03:02.800
<v Speaker 3>but I'm not saying that. Hey, maybe we should look

1:03:03.000 --> 1:03:07.120
<v Speaker 3>into how effective saying my work be with you is

1:03:07.400 --> 1:03:11.720
<v Speaker 3>for treating HPV or like mice tails for rabies or something.

1:03:12.440 --> 1:03:17.160
<v Speaker 3>But it is a good reminder that every generation thinks

1:03:17.360 --> 1:03:21.680
<v Speaker 3>of themselves as being so advanced and looks down on

1:03:21.800 --> 1:03:25.560
<v Speaker 3>past generations with scorn like how on earth could they

1:03:25.600 --> 1:03:29.280
<v Speaker 3>have believed something like that? And so maybe we shouldn't

1:03:29.320 --> 1:03:32.840
<v Speaker 3>be so quick to dismiss the ideas of the past.

1:03:33.000 --> 1:03:35.440
<v Speaker 3>And this is I'm super guilty of this, of like,

1:03:36.080 --> 1:03:38.240
<v Speaker 3>how look at these cures? These are ridiculous.

1:03:38.520 --> 1:03:40.760
<v Speaker 2>I know we all need to be more open minded,

1:03:40.800 --> 1:03:41.440
<v Speaker 2>don't we.

1:03:41.440 --> 1:03:42.560
<v Speaker 4>We do? I think so.

1:03:43.000 --> 1:03:47.960
<v Speaker 3>Yeah, And even if they are clearly not based in

1:03:48.240 --> 1:03:50.760
<v Speaker 3>any sort of medicine or like clearly they would not

1:03:50.760 --> 1:03:53.520
<v Speaker 3>be effective, I think it also is still useful to

1:03:53.960 --> 1:03:56.720
<v Speaker 3>at the very least try to understand the logic or

1:03:56.760 --> 1:04:01.560
<v Speaker 3>reasoning behind them. Why mice tails ground with wine or

1:04:01.680 --> 1:04:05.400
<v Speaker 3>pigeon heart and beer or something like that, Like, right,

1:04:05.520 --> 1:04:09.600
<v Speaker 3>what about that? Because if there's one thing that's an

1:04:09.640 --> 1:04:13.680
<v Speaker 3>absolute certainty it's that future generations will look back on

1:04:13.960 --> 1:04:17.960
<v Speaker 3>us now in our medical practices or scientific knowledge that's

1:04:18.040 --> 1:04:21.760
<v Speaker 3>widely accepted today, and they'll think, how on earth could

1:04:21.760 --> 1:04:24.000
<v Speaker 3>they have thought that? Or oh, my god, did they

1:04:24.040 --> 1:04:26.560
<v Speaker 3>not realize that they were only making things worse?

1:04:27.720 --> 1:04:30.000
<v Speaker 2>I think that almost every day, Yarin Ah.

1:04:30.160 --> 1:04:34.360
<v Speaker 3>Yeah. And the examples of this, I think are endless,

1:04:34.480 --> 1:04:39.720
<v Speaker 3>like our limited understanding of autoimmune disorders, or the mechanisms

1:04:39.840 --> 1:04:43.520
<v Speaker 3>behind different mental health issues, or some of the ways

1:04:43.520 --> 1:04:47.560
<v Speaker 3>that we treat cancer, or how we over use antibiotics. Like,

1:04:47.840 --> 1:04:50.800
<v Speaker 3>there's a lot there that people will have. There's ample

1:04:50.840 --> 1:04:53.560
<v Speaker 3>material for people to laugh at us in the future.

1:04:54.640 --> 1:04:55.919
<v Speaker 3>But we think we know it all now.

1:04:56.440 --> 1:04:58.360
<v Speaker 2>We're all just doing our best.

1:04:58.600 --> 1:05:01.520
<v Speaker 3>We're all just doing our best. But my point is,

1:05:01.680 --> 1:05:04.680
<v Speaker 3>I think that we can look back and see how

1:05:04.720 --> 1:05:08.400
<v Speaker 3>far we've come with these things with our knowledge and technology,

1:05:09.040 --> 1:05:11.640
<v Speaker 3>and maybe feel okay, laughing a bit about my warp

1:05:11.680 --> 1:05:13.760
<v Speaker 3>be with you, just because it's such a great saying.

1:05:14.320 --> 1:05:16.640
<v Speaker 3>But I think we also need to recognize that there

1:05:16.680 --> 1:05:19.960
<v Speaker 3>is still so far to go, and that scientific or

1:05:20.000 --> 1:05:23.760
<v Speaker 3>medical advancements are rarely, if ever, done in leaps and bounds,

1:05:24.160 --> 1:05:28.560
<v Speaker 3>but rather the accumulation of years and years and centuries,

1:05:28.600 --> 1:05:36.400
<v Speaker 3>sometimes of shared knowledge being built. All right, so soapbox moment.

1:05:39.160 --> 1:05:43.080
<v Speaker 3>Beyond those early descriptions of yellow soup and poop as

1:05:43.120 --> 1:05:46.440
<v Speaker 3>treatment from China, there are a couple of other examples

1:05:46.560 --> 1:05:50.720
<v Speaker 3>of what is essentially fecal microbiota transplants from other parts

1:05:50.760 --> 1:05:54.840
<v Speaker 3>of the world. In the seventeenth century, there was an

1:05:54.880 --> 1:05:59.040
<v Speaker 3>Italian anatomist who wrote, quote, I have heard of animals

1:05:59.080 --> 1:06:03.160
<v Speaker 3>which lose the capait to ruminate, which when one puts

1:06:03.200 --> 1:06:05.960
<v Speaker 3>into their mouth a portion of the materials from the

1:06:06.000 --> 1:06:09.240
<v Speaker 3>mouth of another ruminant which that animal has already chewed,

1:06:09.680 --> 1:06:14.120
<v Speaker 3>they immediately start chewing and recover their former health. And

1:06:14.160 --> 1:06:19.760
<v Speaker 3>he called that process transformation. And also, like, I just

1:06:19.760 --> 1:06:23.440
<v Speaker 3>want to point out that many animals regularly consume feces

1:06:23.880 --> 1:06:26.400
<v Speaker 3>for oh, probably a variety of reasons.

1:06:26.520 --> 1:06:27.440
<v Speaker 4>My dog loves it.

1:06:27.840 --> 1:06:33.600
<v Speaker 3>Yeah, dogs love poop. And then later on in the

1:06:33.680 --> 1:06:39.200
<v Speaker 3>seventeenth century, also a German physician recommended fecal transplant for

1:06:39.320 --> 1:06:44.000
<v Speaker 3>humans in a book whose title translates to either healing

1:06:44.120 --> 1:06:49.720
<v Speaker 3>mud pharmacy or salutary filth pharmacy, depending on the source. Like,

1:06:49.760 --> 1:06:53.320
<v Speaker 3>I found it translated both ways, so I don't know.

1:06:54.480 --> 1:06:58.480
<v Speaker 3>I also saw it mentioned that Bedouin groups historically consumed

1:06:58.520 --> 1:07:03.000
<v Speaker 3>camel stools as treatment for bacterial dysentery, something that seems

1:07:03.000 --> 1:07:05.120
<v Speaker 3>to have been picked up on during World War Two,

1:07:05.600 --> 1:07:10.000
<v Speaker 3>when German soldiers were dying of dysentery in Africa, Nazi

1:07:10.040 --> 1:07:13.920
<v Speaker 3>scientists observed that locals would consume fresh camel stools at

1:07:13.920 --> 1:07:16.720
<v Speaker 3>the first sign of disease, and it seemed to prevent

1:07:16.840 --> 1:07:20.640
<v Speaker 3>them from getting sick. And so the scientists cultured what

1:07:20.680 --> 1:07:24.240
<v Speaker 3>they could find in the stools, and they isolated Bascilla subtilis,

1:07:24.760 --> 1:07:28.640
<v Speaker 3>which they cultured and administered to decent success. Like it

1:07:28.720 --> 1:07:32.360
<v Speaker 3>seemed to work to a certain extent, So that's kind

1:07:32.360 --> 1:07:35.000
<v Speaker 3>of cool. It's like this all goes way back further

1:07:35.040 --> 1:07:38.320
<v Speaker 3>than I thought. Yeah, But from then, as far as

1:07:38.320 --> 1:07:42.400
<v Speaker 3>I can tell, the concept of fecal microbiota transplantation it

1:07:42.480 --> 1:07:46.600
<v Speaker 3>really only remained mostly in practice or even in experimentation

1:07:47.280 --> 1:07:52.400
<v Speaker 3>in veterinary medicine until nineteen fifty eight, when Iceman and

1:07:52.600 --> 1:07:57.720
<v Speaker 3>colleagues successfully used fecal microbiota transplants to treat four people

1:07:57.840 --> 1:08:03.520
<v Speaker 3>with pseudomembranous colitis with antibiotic use, this time fortunately using

1:08:03.520 --> 1:08:06.360
<v Speaker 3>an enema rather than oral application.

1:08:06.400 --> 1:08:08.200
<v Speaker 4>Nineteen fifty eight.

1:08:08.680 --> 1:08:13.760
<v Speaker 3>Yeah. Wow, Yeah, And this kind of just goes like

1:08:13.840 --> 1:08:18.680
<v Speaker 3>to further show that developments are not made in isolation,

1:08:18.880 --> 1:08:21.840
<v Speaker 3>like a lot of there's a lot of background to things,

1:08:22.360 --> 1:08:26.640
<v Speaker 3>because in this study he wrote that quote, most of

1:08:26.680 --> 1:08:30.880
<v Speaker 3>the recently reported cases of pseudomembranous colitis have followed the

1:08:30.960 --> 1:08:35.560
<v Speaker 3>use of oral broad spectrum antibiotics, suggesting that the intestinal

1:08:35.560 --> 1:08:39.360
<v Speaker 3>flora was thus altered to permit the overgrowth of antibiotic

1:08:39.400 --> 1:08:42.560
<v Speaker 3>resistant micrococcus pyogenies within the gut.

1:08:43.120 --> 1:08:44.080
<v Speaker 2>Huh.

1:08:44.120 --> 1:08:47.680
<v Speaker 3>And so, yeah, he didn't get the bacterial species right necessarily,

1:08:47.840 --> 1:08:51.400
<v Speaker 3>but all you have to do is swap out micrococcus

1:08:51.439 --> 1:08:56.479
<v Speaker 3>pyogenies for seed if And he's absolutely right in this

1:08:56.640 --> 1:09:00.640
<v Speaker 3>mechanism of how broad spectrum antibiotics like perfectly set up

1:09:00.680 --> 1:09:05.000
<v Speaker 3>the gut for something to take over. Yeah, but decades

1:09:05.040 --> 1:09:08.720
<v Speaker 3>would pass before the idea of the fecal microbiotic transplant

1:09:08.920 --> 1:09:12.840
<v Speaker 3>would gain any real traction in human medicine, especially as

1:09:12.920 --> 1:09:16.240
<v Speaker 3>more antibiotic classes were discovered. Being like, oh, well we

1:09:16.280 --> 1:09:18.160
<v Speaker 3>can fix that, Oh we can fix that this way.

1:09:18.200 --> 1:09:18.439
<v Speaker 4>You know.

1:09:19.360 --> 1:09:21.240
<v Speaker 3>It kind of reminds me a bit of like how

1:09:21.479 --> 1:09:28.200
<v Speaker 3>phage therapy dropped out. Yes, yeah, and it was used again.

1:09:28.680 --> 1:09:33.760
<v Speaker 3>Fecal microbida transplants were used again in nineteen eighty nine

1:09:33.880 --> 1:09:37.559
<v Speaker 3>to treat someone with refractory alterative colitis, and it was

1:09:37.600 --> 1:09:42.720
<v Speaker 3>remarkably successful with lasting recovery. But for the most part,

1:09:42.880 --> 1:09:47.360
<v Speaker 3>reports of people successfully using fecal microbiotic transplants were kind

1:09:47.400 --> 1:09:50.080
<v Speaker 3>of like one offs, like these, you know, case studies

1:09:50.200 --> 1:09:54.480
<v Speaker 3>of people trying out fecal microbida transplants for a variety

1:09:54.560 --> 1:09:58.240
<v Speaker 3>of infectious and non infectious conditions on one patient, on

1:09:58.280 --> 1:10:02.000
<v Speaker 3>a handful of patients, but not like large scale. It

1:10:02.080 --> 1:10:07.000
<v Speaker 3>wasn't until twenty thirteen that the first randomized clinical trial

1:10:07.160 --> 1:10:10.560
<v Speaker 3>was conducted in the Netherlands to look at fecal microbiota

1:10:10.600 --> 1:10:15.040
<v Speaker 3>transplant as a treatment for sea diiff infections. Here's where

1:10:15.040 --> 1:10:18.880
<v Speaker 3>our two our villain and our hero meet took a while,

1:10:18.920 --> 1:10:23.000
<v Speaker 3>but hey, and you'll see that it soon is resolved

1:10:23.600 --> 1:10:27.400
<v Speaker 3>because in this study the participants all had recurren se

1:10:27.520 --> 1:10:31.120
<v Speaker 3>diff and they were all randomly assigned to one of

1:10:31.240 --> 1:10:36.519
<v Speaker 3>three groups, either receiving vancom iosin alone, vancom iasin with

1:10:36.600 --> 1:10:42.080
<v Speaker 3>bowel levage, or bowl levage, and then fecal microbiota transplant

1:10:42.240 --> 1:10:46.439
<v Speaker 3>as treatment. And although the study was initially supposed to

1:10:46.439 --> 1:10:49.439
<v Speaker 3>include one hundred and twenty people with forty people in

1:10:49.479 --> 1:10:54.120
<v Speaker 3>each group, it was stopped early with only forty three participants.

1:10:55.120 --> 1:11:00.240
<v Speaker 3>Why was it stopped because it was so incredibly successful

1:11:00.280 --> 1:11:03.519
<v Speaker 3>that it wasn't ethical to keep going with the other

1:11:03.600 --> 1:11:08.960
<v Speaker 3>control groups when fecal microbiotic transplant showed such incredible cure rates.

1:11:09.400 --> 1:11:10.280
<v Speaker 4>Wow.

1:11:10.760 --> 1:11:15.040
<v Speaker 3>Yeah, So of the nineteen people in the fecal microbiota

1:11:15.120 --> 1:11:21.120
<v Speaker 3>transplant group, ninety four percent were cured of sea diff infection. Wow,

1:11:21.479 --> 1:11:23.840
<v Speaker 3>after a couple rounds of treatment of like eighty something

1:11:23.880 --> 1:11:28.280
<v Speaker 3>were cured after one ninety four percent cured cured.

1:11:28.479 --> 1:11:31.560
<v Speaker 2>And that means like no more recurrences.

1:11:31.000 --> 1:11:35.479
<v Speaker 3>No more recurrences, compared to thirty one percent of those

1:11:35.560 --> 1:11:38.920
<v Speaker 3>in vancomized and only groups and twenty three percent of

1:11:38.960 --> 1:11:43.559
<v Speaker 3>those in the vancomizon plus bowel levage groups. So like, yeah,

1:11:43.640 --> 1:11:49.160
<v Speaker 3>I mean leaps and bounds beyond Yeah, the ability of antibiotics.

1:11:49.160 --> 1:11:52.799
<v Speaker 3>So that's I just I love that. What a clear

1:11:52.960 --> 1:11:58.000
<v Speaker 3>indication of like, hey, there's real promise here. Yeah. And

1:11:58.160 --> 1:12:00.320
<v Speaker 3>after the study was stopped, the people who we're in

1:12:00.320 --> 1:12:04.519
<v Speaker 3>the vancomycin groups were treated with fecal transplants, and they

1:12:04.600 --> 1:12:10.360
<v Speaker 3>also showed high rates of cure. But how exactly do

1:12:10.800 --> 1:12:16.000
<v Speaker 3>they work? How do fecal microbiota transplants work, What diseases

1:12:16.120 --> 1:12:19.639
<v Speaker 3>or conditions do they seem to be effective against? How

1:12:19.640 --> 1:12:22.880
<v Speaker 3>does one become a stool donor what makes someone a

1:12:22.920 --> 1:12:28.280
<v Speaker 3>good candidate for fecal microbida transplants? Are their long term consequences.

1:12:29.000 --> 1:12:29.800
<v Speaker 4>We have so.

1:12:29.920 --> 1:12:36.360
<v Speaker 3>Many questions about fecal microbiota transplantation, and thank goodness we

1:12:36.560 --> 1:12:40.600
<v Speaker 3>have an actual expert to help us answer them. But

1:12:40.760 --> 1:12:43.360
<v Speaker 3>before we get to that, I think that Aaron, I

1:12:43.400 --> 1:12:46.200
<v Speaker 3>want you to tell me just how much the world

1:12:46.360 --> 1:12:52.320
<v Speaker 3>needs creative solutions like fecal microbida transplants for this incredibly

1:12:52.600 --> 1:12:55.080
<v Speaker 3>enormous global seediff problem.

1:12:56.080 --> 1:13:22.800
<v Speaker 2>I would love to right after this break. So we're

1:13:22.840 --> 1:13:27.400
<v Speaker 2>starting off this season two episodes in a row with

1:13:27.720 --> 1:13:32.760
<v Speaker 2>not great numbers. When it comes to we should have

1:13:32.800 --> 1:13:34.880
<v Speaker 2>thought this, we didn't know.

1:13:35.200 --> 1:13:38.960
<v Speaker 3>Listen, of all of the diseases, I would have expected

1:13:39.160 --> 1:13:40.799
<v Speaker 3>seedift to have good numbers.

1:13:41.160 --> 1:13:46.080
<v Speaker 4>Yeah, I would have. Let me tell you what I've got.

1:13:47.640 --> 1:13:51.240
<v Speaker 2>Estimates in the US and from what I can tell

1:13:51.520 --> 1:13:54.120
<v Speaker 2>these numbers that get thrown around seem to be from

1:13:54.240 --> 1:13:57.440
<v Speaker 2>like twenty eleven is where they're getting these estimates.

1:13:58.040 --> 1:14:01.840
<v Speaker 3>That's a long time ago, like in ten years ago.

1:14:02.000 --> 1:14:05.880
<v Speaker 2>Yeah, yeah, but that's what we're working with here aarin.

1:14:06.840 --> 1:14:11.879
<v Speaker 2>The US estimates about five hundred thousand, half a million

1:14:12.040 --> 1:14:18.200
<v Speaker 2>cases a year and twenty nine thousand deaths due to

1:14:18.320 --> 1:14:23.000
<v Speaker 2>see diff infection. Now, that number in the studies that

1:14:23.080 --> 1:14:26.120
<v Speaker 2>I read was thought to be a huge underestimation, but

1:14:26.200 --> 1:14:29.680
<v Speaker 2>that's still the number that the CDC sites on their website,

1:14:29.680 --> 1:14:32.280
<v Speaker 2>for example today here in twenty twenty one.

1:14:32.520 --> 1:14:34.920
<v Speaker 3>I was going to say, that sounds lower than I

1:14:34.920 --> 1:14:35.679
<v Speaker 3>would have thought.

1:14:36.080 --> 1:14:36.439
<v Speaker 4>Yep.

1:14:37.240 --> 1:14:41.680
<v Speaker 2>The European Center for Disease Prevention and Control in the

1:14:41.720 --> 1:14:45.799
<v Speaker 2>same year twenty eleven was estimating one hundred and twenty

1:14:45.800 --> 1:14:49.080
<v Speaker 2>four thousand cases a year and didn't have a real

1:14:49.240 --> 1:14:54.120
<v Speaker 2>estimate on deaths that I found, wait, all across Europe.

1:14:54.640 --> 1:14:59.960
<v Speaker 2>That was Yeah, the European Center for Disease Prevention and Control. Now,

1:15:00.360 --> 1:15:03.320
<v Speaker 2>I obviously wanted to get better numbers than that, so

1:15:03.479 --> 1:15:07.880
<v Speaker 2>I was trying to find global estimates. I found a

1:15:07.920 --> 1:15:10.640
<v Speaker 2>paper that was a meta analysis from a couple of

1:15:10.720 --> 1:15:14.120
<v Speaker 2>years ago that looked at a whole bunch of different

1:15:14.120 --> 1:15:21.160
<v Speaker 2>papers and calculated an average number of SEADIFF infections for

1:15:21.320 --> 1:15:30.160
<v Speaker 2>every one thousand hospital admissions worldwide. And they calculated an average,

1:15:30.240 --> 1:15:36.200
<v Speaker 2>a global average of two point two five cases of

1:15:36.240 --> 1:15:41.519
<v Speaker 2>SEADIFF infection for every one thousand hospital admissions worldwide. And

1:15:41.560 --> 1:15:46.479
<v Speaker 2>I was like, wait a second, that number doesn't make

1:15:46.479 --> 1:15:47.240
<v Speaker 2>a lot of sense.

1:15:47.600 --> 1:15:48.920
<v Speaker 4>And if you look in.

1:15:48.960 --> 1:15:54.120
<v Speaker 2>That paper at the ranges with which they calculated this average,

1:15:54.720 --> 1:15:59.880
<v Speaker 2>the ranges are bananas. They're from anywhere from one case

1:16:00.120 --> 1:16:04.439
<v Speaker 2>per one thousand to thirty seven cases per one thousand

1:16:04.439 --> 1:16:08.639
<v Speaker 2>hospital admissions, depending on which geographic region you look at.

1:16:09.000 --> 1:16:12.959
<v Speaker 2>North America by far has the greatest number of cases

1:16:13.439 --> 1:16:18.880
<v Speaker 2>reported compared to other places. And even though this study

1:16:18.920 --> 1:16:22.080
<v Speaker 2>looked at forty one different countries, there was no data

1:16:22.080 --> 1:16:26.599
<v Speaker 2>whatsoever from South America, or from Africa, or from a

1:16:26.640 --> 1:16:27.839
<v Speaker 2>lot of countries in Asia.

1:16:28.840 --> 1:16:31.519
<v Speaker 3>So still we don't have great numbers.

1:16:31.640 --> 1:16:33.759
<v Speaker 2>We still don't have great numbers.

1:16:34.160 --> 1:16:36.720
<v Speaker 3>Okay, but the twenty nine thousand deaths and half a

1:16:36.800 --> 1:16:40.960
<v Speaker 3>million cases in the US in twenty eleven was an

1:16:41.080 --> 1:16:45.400
<v Speaker 3>underestimation then and likely continues to be an underestimation.

1:16:45.760 --> 1:16:48.320
<v Speaker 2>Yes, I did a little bit of aerin math.

1:16:48.640 --> 1:16:49.720
<v Speaker 4>You know my trademark.

1:16:49.920 --> 1:16:51.240
<v Speaker 3>I love aerin math.

1:16:51.120 --> 1:16:56.320
<v Speaker 2>Me too, trademark airin math. Don't trust these numbers. So,

1:16:56.560 --> 1:17:00.519
<v Speaker 2>according to the American Hospital Association, and that's just in

1:17:00.560 --> 1:17:05.080
<v Speaker 2>the US, there are over thirty six million hospital admissions

1:17:05.160 --> 1:17:08.439
<v Speaker 2>every year in the US alone. So if you look

1:17:08.439 --> 1:17:10.960
<v Speaker 2>at those estimates of like maybe it's as low as

1:17:11.000 --> 1:17:14.320
<v Speaker 2>two and a half, it isn't cases of seadiff per

1:17:14.360 --> 1:17:19.400
<v Speaker 2>one thousand hospitalizations or as high as thirty seven per

1:17:19.439 --> 1:17:23.639
<v Speaker 2>one thousand. That's anywhere from eighty thousand to over one

1:17:23.680 --> 1:17:29.519
<v Speaker 2>point two million cases in US hospitals alone each year.

1:17:30.000 --> 1:17:33.840
<v Speaker 3>It's quite arranged. Plus it's not just hospitals, Like what

1:17:33.880 --> 1:17:35.440
<v Speaker 3>about long term care facilities?

1:17:35.479 --> 1:17:36.040
<v Speaker 4>Exactly?

1:17:36.280 --> 1:17:39.920
<v Speaker 2>Exactly that's the problem. And we just with a lack

1:17:39.960 --> 1:17:43.320
<v Speaker 2>of surveillance in a lot of places, and sometimes even

1:17:43.360 --> 1:17:46.439
<v Speaker 2>a lack of definitions on how are you testing or

1:17:46.479 --> 1:17:49.960
<v Speaker 2>screening for seadiff infection versus colonization? How are you even

1:17:50.000 --> 1:17:54.959
<v Speaker 2>defining a seadiff infection? It makes global estimates really really difficult.

1:17:55.640 --> 1:17:59.680
<v Speaker 3>Well, I think we can come up with a qualitative

1:17:59.720 --> 1:18:05.719
<v Speaker 3>metric based on the biology of the disease as well

1:18:05.760 --> 1:18:09.200
<v Speaker 3>as our medical practices of you know, using a lot

1:18:09.240 --> 1:18:13.160
<v Speaker 3>of antibiotics for a good reason, right, and that it's

1:18:13.200 --> 1:18:18.240
<v Speaker 3>probably been only increasing since it was very first scene

1:18:18.680 --> 1:18:22.439
<v Speaker 3>and I mean skyrocketed in terms of numbers, and now

1:18:22.479 --> 1:18:25.040
<v Speaker 3>it's everywhere and it's a huge problem.

1:18:25.360 --> 1:18:26.000
<v Speaker 4>It really is.

1:18:26.880 --> 1:18:32.240
<v Speaker 2>So because of that, there are a lot of areas

1:18:32.280 --> 1:18:36.960
<v Speaker 2>of research ongoing when it comes to SEEDFF. Even though

1:18:36.960 --> 1:18:40.240
<v Speaker 2>it seems like future areas, a lot of this research

1:18:40.960 --> 1:18:44.720
<v Speaker 2>is promising enough that there are things that are not

1:18:45.160 --> 1:18:50.840
<v Speaker 2>future future directions of research there present. The very first

1:18:50.880 --> 1:18:56.160
<v Speaker 2>thing is probiotics. Probiotics are an area of research that

1:18:56.200 --> 1:18:58.560
<v Speaker 2>I think is really fascinating. It all goes back to

1:18:58.600 --> 1:19:01.280
<v Speaker 2>the whole microbiome, which we don't know a lot about.

1:19:02.360 --> 1:19:06.240
<v Speaker 2>But there was a Cochrane review from twenty seventeen that

1:19:06.400 --> 1:19:09.679
<v Speaker 2>showed with moderate certainty evidence, which is like pretty good

1:19:09.720 --> 1:19:14.320
<v Speaker 2>for a Cochrane review, that probiotics can reduce the risk

1:19:14.400 --> 1:19:18.600
<v Speaker 2>of seediff infection by as much as sixty percent in

1:19:18.720 --> 1:19:22.960
<v Speaker 2>people who are inpatient in the hospital on antibiotics. So

1:19:23.080 --> 1:19:28.920
<v Speaker 2>giving probiotics concurrently with antibiotics might be significantly protective.

1:19:29.760 --> 1:19:34.320
<v Speaker 3>This is like opening a huge can of worms, but like, yeah.

1:19:34.160 --> 1:19:37.440
<v Speaker 2>I I know, and it was a part review.

1:19:37.880 --> 1:19:39.559
<v Speaker 4>What does that mean exactly?

1:19:40.040 --> 1:19:43.679
<v Speaker 2>I don't have data on like what that actually means

1:19:43.680 --> 1:19:47.760
<v Speaker 2>in practice, because, yeah, probiotics, they're not exactly regulated. We

1:19:47.840 --> 1:19:50.840
<v Speaker 2>don't know enough about the human microbiome to know what

1:19:51.040 --> 1:19:54.360
<v Speaker 2>are these specific bacteria and which probiotics do you take?

1:19:54.400 --> 1:19:56.200
<v Speaker 2>And how much money are you supposed to spend on

1:19:56.240 --> 1:19:57.160
<v Speaker 2>these things.

1:19:57.160 --> 1:19:57.679
<v Speaker 4>Et cetera.

1:19:58.160 --> 1:20:01.120
<v Speaker 3>And things that are claiming to be probiotic, but like are.

1:20:01.000 --> 1:20:04.040
<v Speaker 4>They actually probatic? Right, Like exactly what do.

1:20:04.000 --> 1:20:06.240
<v Speaker 3>You need to do to have probatic on your label?

1:20:07.000 --> 1:20:09.080
<v Speaker 4>That I don't have an answer too.

1:20:09.880 --> 1:20:12.120
<v Speaker 3>But things to think about, things to think about.

1:20:12.400 --> 1:20:16.360
<v Speaker 2>And they did mention yogurt specifically multiple times in this

1:20:16.360 --> 1:20:18.280
<v Speaker 2>that makes sense, So I don't know.

1:20:18.280 --> 1:20:21.120
<v Speaker 3>And I'm also I'm all for probiotics, but me too,

1:20:21.400 --> 1:20:23.400
<v Speaker 3>like we got to ask questions.

1:20:23.880 --> 1:20:26.599
<v Speaker 2>But yeah, so that's kind of a one thing now

1:20:27.080 --> 1:20:29.559
<v Speaker 2>that seems to be really promising, and I don't think

1:20:29.560 --> 1:20:32.080
<v Speaker 2>that it's really talked about enough. And it's likely because

1:20:32.120 --> 1:20:34.200
<v Speaker 2>of all the problems that are inherent, like we already

1:20:34.240 --> 1:20:36.720
<v Speaker 2>said with the idea of probiotics, that we just don't

1:20:36.760 --> 1:20:38.680
<v Speaker 2>have good regulation on them. We don't know a lot

1:20:38.680 --> 1:20:41.639
<v Speaker 2>about them. But that doesn't mean you can't find places

1:20:41.680 --> 1:20:46.360
<v Speaker 2>that have live cultures of bacteria and help yourself. I

1:20:46.400 --> 1:20:52.559
<v Speaker 2>don't know other things there are. Even though antibiotics are

1:20:52.600 --> 1:20:56.120
<v Speaker 2>still used very commonly for treatment of seediff, we know

1:20:56.240 --> 1:20:59.479
<v Speaker 2>that antibiotic resistance is a huge problem. There are a

1:20:59.600 --> 1:21:02.880
<v Speaker 2>number of different monoclonal antibodies that have been shown to

1:21:02.920 --> 1:21:07.400
<v Speaker 2>be beneficial for the treatment of especially recurrent seediff infection.

1:21:08.560 --> 1:21:11.559
<v Speaker 2>That would be something that's only available, you know, in

1:21:11.600 --> 1:21:13.840
<v Speaker 2>the case where you're already really, really sick. It's not

1:21:13.880 --> 1:21:18.200
<v Speaker 2>necessarily preventing you. There are also a lot of different

1:21:18.280 --> 1:21:23.200
<v Speaker 2>vaccine candidates that have been studied. Generally these are toxoid vaccines,

1:21:23.479 --> 1:21:27.200
<v Speaker 2>so vaccines against just the toxins A and B to

1:21:27.400 --> 1:21:33.479
<v Speaker 2>help prevent infection from seediff rather than just colonization. But yeah,

1:21:33.520 --> 1:21:37.200
<v Speaker 2>there's a lot of promise both in terms of how

1:21:37.240 --> 1:21:41.599
<v Speaker 2>we can potentially deal with especially severe seaediff infections today

1:21:41.760 --> 1:21:45.519
<v Speaker 2>but going forward, how we might be able to prevent

1:21:45.560 --> 1:21:51.000
<v Speaker 2>them even more down the line. But here on TPDKY,

1:21:51.200 --> 1:21:54.400
<v Speaker 2>we all have our biases, and one of ours is

1:21:54.479 --> 1:21:58.479
<v Speaker 2>how amazing fecal microbiotic transplantation is.

1:21:58.960 --> 1:22:01.200
<v Speaker 3>Yeh, I don't think we've been in enthusiastic enough about

1:22:01.240 --> 1:22:02.520
<v Speaker 3>it this episode.

1:22:02.760 --> 1:22:05.320
<v Speaker 4>It is truly like the first time that.

1:22:05.280 --> 1:22:08.640
<v Speaker 2>I heard about it, I was just so enthused, like

1:22:08.760 --> 1:22:12.280
<v Speaker 2>I want to be a donor and or I want

1:22:12.720 --> 1:22:15.639
<v Speaker 2>a transplant for just because I think it's amazing.

1:22:16.200 --> 1:22:19.320
<v Speaker 3>I think it's it is like you said, it's just

1:22:19.400 --> 1:22:22.920
<v Speaker 3>like you know, Chef's kiss. Yes, beautiful.

1:22:23.040 --> 1:22:23.599
<v Speaker 4>I love it.

1:22:23.720 --> 1:22:27.799
<v Speaker 2>So we were absolutely thrilled to speak with a true

1:22:27.840 --> 1:22:32.680
<v Speaker 2>expert from Open Biome, which is a nonprofit organization that

1:22:32.960 --> 1:22:38.160
<v Speaker 2>is all about expanding access safe access to fecal microbiota

1:22:38.200 --> 1:22:41.680
<v Speaker 2>transplant and increasing research into.

1:22:41.479 --> 1:22:42.920
<v Speaker 4>The human microbiome.

1:22:43.720 --> 1:22:46.360
<v Speaker 2>We'll let them introduce themselves right now.

1:22:48.439 --> 1:22:52.200
<v Speaker 6>I'm Majdi. I am the chief medical officer at open Biome,

1:22:52.360 --> 1:22:57.400
<v Speaker 6>and I'm a physician trained in infectious diseases, as you

1:22:57.400 --> 1:22:59.679
<v Speaker 6>could probably tell by the accent, trained in the UK,

1:23:00.320 --> 1:23:05.840
<v Speaker 6>and my first encounter with FMT was about ten years

1:23:05.880 --> 1:23:09.639
<v Speaker 6>ago now and a patient who an elderly woman who

1:23:10.160 --> 1:23:14.080
<v Speaker 6>had seed of facial infection after a hip operation and

1:23:14.200 --> 1:23:17.000
<v Speaker 6>we'd run out of options for her. The sort of

1:23:17.080 --> 1:23:22.000
<v Speaker 6>next thing on the treatment ladder was surgery, which for

1:23:22.160 --> 1:23:25.160
<v Speaker 6>a frail patient like this was going to come with

1:23:25.200 --> 1:23:28.439
<v Speaker 6>a lot of risks, and so this was before stool banks.

1:23:28.840 --> 1:23:32.639
<v Speaker 6>We had to do the FMT ourselves from a related

1:23:32.680 --> 1:23:36.200
<v Speaker 6>donor of the patient, and you know, within three days

1:23:36.240 --> 1:23:38.960
<v Speaker 6>the patient had fully recovered from their seed iff and

1:23:39.160 --> 1:23:42.360
<v Speaker 6>was eating and ready to go home. So that was

1:23:42.400 --> 1:23:45.519
<v Speaker 6>sort of my first encounter with this treatment. It wasn't

1:23:45.600 --> 1:23:48.000
<v Speaker 6>until I came to the US that and met the

1:23:48.040 --> 1:23:50.400
<v Speaker 6>team at Opened Biome just as things were getting started

1:23:50.439 --> 1:23:53.960
<v Speaker 6>that I ended up embarking on this adventure.

1:23:54.360 --> 1:23:59.200
<v Speaker 3>Yeah, that's amazing. So talking now about open Biome, can

1:23:59.240 --> 1:24:02.280
<v Speaker 3>you tell us a about the project and sort of

1:24:02.320 --> 1:24:05.080
<v Speaker 3>what a nonprofit stool bank is, you know, how did

1:24:05.120 --> 1:24:07.479
<v Speaker 3>it get started and what are some of its missions?

1:24:08.080 --> 1:24:11.439
<v Speaker 6>Yeah, yeah, so open bind we're a nonprofit stool bank.

1:24:11.479 --> 1:24:14.120
<v Speaker 6>As he said, you know, our first mission is to

1:24:14.320 --> 1:24:18.200
<v Speaker 6>enable safe access to this treatment fecal microbarri to transplants

1:24:18.280 --> 1:24:21.640
<v Speaker 6>or FMT, and the second half of our mission is

1:24:21.680 --> 1:24:25.160
<v Speaker 6>to castalyize research in the human gut microbiome using FMT,

1:24:25.400 --> 1:24:29.320
<v Speaker 6>but also other tools in our toolkit to support new

1:24:29.360 --> 1:24:33.120
<v Speaker 6>ways of understanding and treating diseases, especially those in areas

1:24:33.120 --> 1:24:37.160
<v Speaker 6>of unmet need. And we started really because of our

1:24:37.360 --> 1:24:41.120
<v Speaker 6>executive director Carolyn. She had a relative that, you know,

1:24:41.160 --> 1:24:44.799
<v Speaker 6>a young guy in his early twenties, just out of college,

1:24:44.920 --> 1:24:47.760
<v Speaker 6>you know, had a gold badder infection, had surgery and

1:24:47.760 --> 1:24:52.880
<v Speaker 6>then some antibiotics after that, and developed cedificile infection and eventually,

1:24:53.280 --> 1:24:55.200
<v Speaker 6>you know, having found out that he would have had

1:24:55.240 --> 1:24:57.840
<v Speaker 6>to wait several months for an FMT, he would have

1:24:57.880 --> 1:25:01.280
<v Speaker 6>had to drive hours to one of hospitals in New

1:25:01.360 --> 1:25:04.920
<v Speaker 6>York to get this treatment, decided to take matters into

1:25:05.000 --> 1:25:08.080
<v Speaker 6>his own hands and ended up doing an FMT himself.

1:25:08.880 --> 1:25:12.240
<v Speaker 6>And so, you know, that was sort of the motivating

1:25:12.320 --> 1:25:15.879
<v Speaker 6>patient in a way for us to establish Open Biome

1:25:16.400 --> 1:25:20.200
<v Speaker 6>really to make sure that patients who had seedificil infection,

1:25:20.720 --> 1:25:24.040
<v Speaker 6>who had failed antibiotic therapy didn't have to go through

1:25:24.040 --> 1:25:27.240
<v Speaker 6>that process again of having to source their own donor

1:25:27.600 --> 1:25:30.920
<v Speaker 6>and getting their own treatment arranged, and to make this,

1:25:31.000 --> 1:25:34.640
<v Speaker 6>as you know, as straightforward as getting a blood transfusion.

1:25:35.240 --> 1:25:37.160
<v Speaker 6>And so you know, we set ourselves up really to

1:25:37.600 --> 1:25:42.800
<v Speaker 6>serve that need. And yeah, we've grown to the point

1:25:42.800 --> 1:25:46.320
<v Speaker 6>now where we work with over a thousand hospitals across

1:25:46.360 --> 1:25:49.480
<v Speaker 6>the US and ninety nine percent of the US population

1:25:49.680 --> 1:25:52.759
<v Speaker 6>is within a four hour drive of a hospital. Using

1:25:52.960 --> 1:25:54.640
<v Speaker 6>open FMT.

1:25:55.200 --> 1:25:59.519
<v Speaker 3>That is amazing. What an origin story. I can't believe that,

1:26:00.479 --> 1:26:03.200
<v Speaker 3>but I mean it's clear that over the years the

1:26:03.240 --> 1:26:06.680
<v Speaker 3>need for FMT's is more and more pressing. And so

1:26:06.840 --> 1:26:09.880
<v Speaker 3>it's an incredible thing that you guys are doing. And

1:26:09.920 --> 1:26:14.200
<v Speaker 3>So before we get further into the transplant aspect of this,

1:26:14.400 --> 1:26:17.760
<v Speaker 3>I want to talk about donation, like what is a

1:26:17.800 --> 1:26:21.519
<v Speaker 3>stool bank and also how does one become a donor?

1:26:21.520 --> 1:26:23.880
<v Speaker 3>What are their criteria for acceptance? Like I have a

1:26:23.920 --> 1:26:25.679
<v Speaker 3>lot of questions, but we'll start there.

1:26:26.840 --> 1:26:30.000
<v Speaker 6>Yeah, sure, think so the stool bank is a bit

1:26:30.040 --> 1:26:32.960
<v Speaker 6>like a blood bank really, but for poop. So what

1:26:33.040 --> 1:26:35.960
<v Speaker 6>we do is we screen our donors. We're based in

1:26:36.000 --> 1:26:39.000
<v Speaker 6>Boston and so all of our donors come from around

1:26:39.000 --> 1:26:42.080
<v Speaker 6>this area. A bit like with a blood transfusion, we

1:26:42.160 --> 1:26:44.679
<v Speaker 6>would screen our donors to make sure that they aren't

1:26:44.760 --> 1:26:48.479
<v Speaker 6>potentially passing on any risk of either infection to a

1:26:48.560 --> 1:26:52.240
<v Speaker 6>recipient or potentially some of these other diseases that we

1:26:52.400 --> 1:26:55.880
<v Speaker 6>seem to see in association with the gut microbiome. You know,

1:26:55.920 --> 1:27:01.160
<v Speaker 6>these are things like asthma, diabetes, obesity, even mood disorders

1:27:01.160 --> 1:27:05.440
<v Speaker 6>like depression or anxiety. And so you know, we put

1:27:05.479 --> 1:27:08.799
<v Speaker 6>these donors through a pretty comprehensive screening process, which starts

1:27:08.840 --> 1:27:11.840
<v Speaker 6>off initially with an online form that if anyone is

1:27:11.880 --> 1:27:14.120
<v Speaker 6>interested in becoming a donor, they go to our website

1:27:14.720 --> 1:27:17.400
<v Speaker 6>fill out a short form that excludes for the common

1:27:17.439 --> 1:27:21.000
<v Speaker 6>reasons that folks are ineligible to become a donor. And

1:27:21.040 --> 1:27:24.120
<v Speaker 6>so then if a prospective donor completes that form and

1:27:24.360 --> 1:27:28.120
<v Speaker 6>it's all clear, then they would be invited for an

1:27:28.120 --> 1:27:31.280
<v Speaker 6>in person clinical assessment led by one of our clinical

1:27:31.280 --> 1:27:35.519
<v Speaker 6>team that includes a clinical assessment where they run through

1:27:35.840 --> 1:27:40.520
<v Speaker 6>nearly two hundred questions related to their health, physical assessment,

1:27:41.000 --> 1:27:43.720
<v Speaker 6>and then if they pass that, they go through a

1:27:43.920 --> 1:27:47.240
<v Speaker 6>blood and a stall test, and yeah, it doesn't stop

1:27:47.240 --> 1:27:50.120
<v Speaker 6>there though, you know. If a donor passes all of that,

1:27:50.240 --> 1:27:53.160
<v Speaker 6>then they have an assessment each time they drop off

1:27:53.160 --> 1:27:57.360
<v Speaker 6>a stall sample, and then every sixty days they undergo

1:27:57.439 --> 1:28:00.200
<v Speaker 6>the same three step screen. So the clinical all the

1:28:00.200 --> 1:28:03.000
<v Speaker 6>blood in the stool. The past rate for becoming a

1:28:03.080 --> 1:28:07.400
<v Speaker 6>donor is less than three percent, and so we often

1:28:07.439 --> 1:28:10.200
<v Speaker 6>say that it's harder to become a donor open biome

1:28:10.240 --> 1:28:12.400
<v Speaker 6>than it is to say, get into MIT or HAVID

1:28:12.680 --> 1:28:15.440
<v Speaker 6>because we are sort of screening these folks really rigorously.

1:28:15.920 --> 1:28:19.599
<v Speaker 3>Wow, that is very interesting. What a thorough process. I mean,

1:28:19.640 --> 1:28:22.720
<v Speaker 3>it completely makes sense. But so now I want to

1:28:22.800 --> 1:28:29.080
<v Speaker 3>switch to transplants. What are FMT's fecal microbiotic transplants and

1:28:29.439 --> 1:28:32.000
<v Speaker 3>how do they work? Could you walk us through like

1:28:32.040 --> 1:28:34.720
<v Speaker 3>the entire process from the patient's perspective.

1:28:35.200 --> 1:28:40.040
<v Speaker 6>Sure, So, a fecal microbiot to transplant or an FMT

1:28:40.320 --> 1:28:43.040
<v Speaker 6>is a very simple treatment in a lot of ways.

1:28:43.120 --> 1:28:47.240
<v Speaker 6>It's essentially taking stool from a healthy donor and transferring

1:28:47.280 --> 1:28:50.160
<v Speaker 6>it to a patient who's got a disease, in this

1:28:50.240 --> 1:28:54.000
<v Speaker 6>case ceoficile infection. And you know, when a donor who's

1:28:54.000 --> 1:28:57.080
<v Speaker 6>been screened and gone through that very rigorous process provides

1:28:57.120 --> 1:29:02.080
<v Speaker 6>a sample, that sample is inspected, tested, and then simply

1:29:02.200 --> 1:29:07.120
<v Speaker 6>we add a saline glyceryl buffer so that it stays stable.

1:29:07.200 --> 1:29:11.040
<v Speaker 6>Once it's frozen, we homogenize it or blend it and

1:29:11.080 --> 1:29:15.559
<v Speaker 6>then filter it to remove any anything like food debris

1:29:16.120 --> 1:29:19.680
<v Speaker 6>or other things that aren't relevant for the treatment. And

1:29:19.760 --> 1:29:24.040
<v Speaker 6>so then that treatment gets frozen, either as a liquid

1:29:24.240 --> 1:29:29.040
<v Speaker 6>preparation that is instilled via colonoscopy or via a par

1:29:29.120 --> 1:29:33.800
<v Speaker 6>endoscopy or nasogastric tube, or alternatively we prepare it into capsules,

1:29:34.360 --> 1:29:37.599
<v Speaker 6>and these capsules can be taken by the patient at

1:29:37.600 --> 1:29:42.160
<v Speaker 6>their doctor's office, and the patients are observed for several

1:29:42.200 --> 1:29:45.439
<v Speaker 6>hours afterwards, and then they can usually start eating four

1:29:45.439 --> 1:29:48.920
<v Speaker 6>to six hours afterwards as well. And then in many cases,

1:29:49.280 --> 1:29:51.920
<v Speaker 6>patients are discharged on the same day so they're able

1:29:51.960 --> 1:29:54.400
<v Speaker 6>to go home. And you know, one thing we are

1:29:54.520 --> 1:29:58.960
<v Speaker 6>really keen on emphasizing it open biome is prevention of

1:29:59.080 --> 1:30:02.320
<v Speaker 6>cediff when patients go home, you know, making sure that

1:30:02.320 --> 1:30:05.040
<v Speaker 6>their home is clean, making sure that high touch surfaces

1:30:05.840 --> 1:30:08.919
<v Speaker 6>are cleaned so that they're not re exposing themselves to seediff,

1:30:09.320 --> 1:30:12.400
<v Speaker 6>and you know where possible, avoiding antibiotics as well, or

1:30:12.439 --> 1:30:14.800
<v Speaker 6>having a conversation with their physician that they've had an

1:30:14.840 --> 1:30:18.360
<v Speaker 6>FMT might be at risk of sediff. So yeah, you know,

1:30:18.560 --> 1:30:21.599
<v Speaker 6>the treatment itself is surprisingly straightforward in many ways, but

1:30:21.960 --> 1:30:25.559
<v Speaker 6>I think the complexity is around the donus screening and

1:30:25.640 --> 1:30:28.960
<v Speaker 6>making sure that the patient is appropriately selected for an

1:30:29.000 --> 1:30:32.560
<v Speaker 6>FMT and that the risks and benefits are clearly communicated

1:30:32.600 --> 1:30:35.360
<v Speaker 6>to them as well before performing the treatment.

1:30:35.920 --> 1:30:41.000
<v Speaker 3>Gotcha, Yeah, that is fascinating. I love the idea of

1:30:41.360 --> 1:30:45.040
<v Speaker 3>pills just like a little capsule of and here's a

1:30:45.080 --> 1:30:48.439
<v Speaker 3>new microbiome for your gut. Like that's it just feels

1:30:48.439 --> 1:30:52.839
<v Speaker 3>like the future. And so that actually your last comment

1:30:52.840 --> 1:30:56.600
<v Speaker 3>there leads me to my next question, which is about eligibility.

1:30:57.000 --> 1:31:00.400
<v Speaker 3>As you mentioned, unfortunately, not everyone who has a C.

1:31:00.560 --> 1:31:04.519
<v Speaker 3>Deficile infection is eligible for an FMT, So I wanted

1:31:04.560 --> 1:31:07.880
<v Speaker 3>to ask what are the criteria for eligibility and who

1:31:07.920 --> 1:31:08.519
<v Speaker 3>decides it.

1:31:09.040 --> 1:31:13.640
<v Speaker 6>So FMT is recommended for patients with C deficile that

1:31:13.840 --> 1:31:17.240
<v Speaker 6>haven't responded to antibiotic therapy, and that's the only patient

1:31:17.280 --> 1:31:20.000
<v Speaker 6>group that this treatment is recommended for at the moment.

1:31:20.760 --> 1:31:23.920
<v Speaker 6>And so, you know, four hundred and sixty thousand Americans

1:31:24.000 --> 1:31:28.200
<v Speaker 6>experience C deficile every year. Of those, about twenty to

1:31:28.280 --> 1:31:31.439
<v Speaker 6>thirty five percent of film will experience a recurrence of

1:31:31.479 --> 1:31:35.920
<v Speaker 6>that infection. And then potentially, you know, from that population,

1:31:36.080 --> 1:31:39.960
<v Speaker 6>about forty to sixty percent will experience a second recurrence.

1:31:40.560 --> 1:31:43.759
<v Speaker 6>And it's on that second recurrence of their C. Deficile

1:31:43.800 --> 1:31:48.519
<v Speaker 6>infection that they are eligible for in FMT. The other

1:31:48.560 --> 1:31:54.120
<v Speaker 6>consideration is, you know, FMT is still an investigational drug,

1:31:54.200 --> 1:31:56.800
<v Speaker 6>and what that means is that it has not gone

1:31:56.840 --> 1:32:01.519
<v Speaker 6>through the FDA approval process. And there remains some unknowns

1:32:01.560 --> 1:32:05.439
<v Speaker 6>about the treatment itself, and so at this stage, in

1:32:05.520 --> 1:32:09.000
<v Speaker 6>a relatively early time in the field, it's important to

1:32:09.000 --> 1:32:12.320
<v Speaker 6>make sure that patients, especially those who are immunocompromised, for example,

1:32:12.760 --> 1:32:17.000
<v Speaker 6>children or you know, those in pregnancy perhaps are carefully

1:32:17.040 --> 1:32:20.479
<v Speaker 6>considered for FMT. And in some patients they may not

1:32:20.520 --> 1:32:23.680
<v Speaker 6>be eligible because of perhaps one of those reasons that

1:32:23.800 --> 1:32:27.559
<v Speaker 6>mean the risk benefit of that FMT treatment doesn't make

1:32:27.600 --> 1:32:30.639
<v Speaker 6>sense in their case. So, you know, those are the

1:32:30.680 --> 1:32:34.840
<v Speaker 6>main criteria really for an FMT, and I think over

1:32:34.920 --> 1:32:38.080
<v Speaker 6>time we'll be refining those, hopefully both to enhance the

1:32:38.080 --> 1:32:40.680
<v Speaker 6>safety of the treatment and also to improve the efficacy

1:32:40.720 --> 1:32:43.480
<v Speaker 6>as well of each treatment that's administered.

1:32:44.960 --> 1:32:47.800
<v Speaker 3>Yeah, and so you know, you mentioned that there are

1:32:47.840 --> 1:32:52.960
<v Speaker 3>some risks associated with fmts, both short term and potentially

1:32:53.000 --> 1:32:55.920
<v Speaker 3>long term. For instance, there's a lot that we still

1:32:56.000 --> 1:33:00.880
<v Speaker 3>don't know about how our gut microbiota affect are risk

1:33:00.960 --> 1:33:05.160
<v Speaker 3>of developing some chronic conditions, right like cancer, diabetes, heart disease.

1:33:05.400 --> 1:33:07.479
<v Speaker 3>I mean, many studies have shown a link, but what

1:33:07.520 --> 1:33:10.400
<v Speaker 3>that link actually means is that correlative, is it causative?

1:33:10.800 --> 1:33:14.720
<v Speaker 3>It's unclear, And so could you walk us through some

1:33:14.960 --> 1:33:18.599
<v Speaker 3>of the risks of FMT, both short and long term,

1:33:18.800 --> 1:33:21.280
<v Speaker 3>or maybe what you see as the biggest gaps in

1:33:21.400 --> 1:33:22.639
<v Speaker 3>knowledge regarding risk.

1:33:23.240 --> 1:33:26.360
<v Speaker 6>Yeah, absolutely, so, I think when it comes to risk

1:33:26.439 --> 1:33:30.559
<v Speaker 6>of FFT, you know, it's always quite concept specific. You know,

1:33:30.600 --> 1:33:34.719
<v Speaker 6>in the case of c dificile infection, especially severe disease,

1:33:34.760 --> 1:33:37.880
<v Speaker 6>which carries a very high mortality rate, and where even

1:33:37.960 --> 1:33:44.280
<v Speaker 6>surgery carries a significant rate of morbidity and poor outcomes

1:33:44.439 --> 1:33:48.640
<v Speaker 6>following the surgery, that profile, the risk benefit profile in

1:33:48.680 --> 1:33:52.519
<v Speaker 6>that patient may be very different to someone who is

1:33:52.600 --> 1:33:56.919
<v Speaker 6>very early in their seedff and perhaps has more options

1:33:57.000 --> 1:34:00.720
<v Speaker 6>left on the table, such as antibiotics or BES, tuximab

1:34:01.560 --> 1:34:04.280
<v Speaker 6>or other interventions. So I think the first thing to

1:34:04.720 --> 1:34:08.240
<v Speaker 6>emphasize is that it's very context specific and depends on

1:34:08.280 --> 1:34:11.879
<v Speaker 6>the patient. But more generally speaking, this is a treatment

1:34:11.920 --> 1:34:16.720
<v Speaker 6>that relies on instilling bacteria into a patient. And we

1:34:16.800 --> 1:34:19.240
<v Speaker 6>do all we can, you know, just like a blood

1:34:19.240 --> 1:34:25.360
<v Speaker 6>transfusion to screen out pathogens and bacteria viruses, but you know,

1:34:25.439 --> 1:34:29.160
<v Speaker 6>there is always the potential risk that an infection might

1:34:29.200 --> 1:34:32.640
<v Speaker 6>be transmitted, and you know, COVID has taught us that,

1:34:32.840 --> 1:34:35.599
<v Speaker 6>if you know, we have to continuously be evolving our

1:34:36.040 --> 1:34:39.680
<v Speaker 6>criteria for screening for infections to you assess for new

1:34:39.760 --> 1:34:43.679
<v Speaker 6>infections that might be on the horizon, especially antibiotic resistant ones,

1:34:44.439 --> 1:34:47.240
<v Speaker 6>and also, you know, continuously enhancing the tests that we

1:34:47.400 --> 1:34:50.879
<v Speaker 6>use to screen out pathogens that might be potentially transmitted

1:34:50.920 --> 1:34:55.160
<v Speaker 6>in stall. The second sort of category of risks i'd say,

1:34:55.280 --> 1:34:59.880
<v Speaker 6>are as you said, the potential association with non inf

1:35:00.040 --> 1:35:03.680
<v Speaker 6>anxious diseases. To date, we haven't seen any evidence to

1:35:03.720 --> 1:35:08.479
<v Speaker 6>suggest that FMT transmits any of those conditions or increases

1:35:08.520 --> 1:35:10.840
<v Speaker 6>the risk of those However, I think it's something that

1:35:10.880 --> 1:35:13.280
<v Speaker 6>we have to be very mindful of that we don't

1:35:13.560 --> 1:35:17.439
<v Speaker 6>have much evidence on the long term effects of FMT,

1:35:18.600 --> 1:35:21.639
<v Speaker 6>and so it's really important you know, with the patient

1:35:21.720 --> 1:35:25.080
<v Speaker 6>that the clinician is having a meaningful conversation around the

1:35:25.160 --> 1:35:28.240
<v Speaker 6>risks and the unknowns of some of these long term

1:35:28.760 --> 1:35:32.840
<v Speaker 6>consequences of FMT. But you know, for a patient who

1:35:33.160 --> 1:35:35.120
<v Speaker 6>has run out of all of their treatment options and

1:35:35.360 --> 1:35:40.640
<v Speaker 6>faces potentially resection of their bowel or long term antibiotics,

1:35:40.800 --> 1:35:45.200
<v Speaker 6>or you know, even worse development of really severe disease,

1:35:45.800 --> 1:35:49.160
<v Speaker 6>that sort of risk benefit needs to be taken into consideration.

1:35:50.280 --> 1:35:53.160
<v Speaker 6>You know, there are sort of efforts being made to

1:35:54.720 --> 1:35:58.439
<v Speaker 6>set up registries. So the American College of Gastroentrology has

1:35:58.479 --> 1:36:01.559
<v Speaker 6>set up a patient registry to all the recipients of

1:36:01.640 --> 1:36:04.720
<v Speaker 6>FMT to ten years. And I think that's going to

1:36:04.760 --> 1:36:08.880
<v Speaker 6>be really helpful in understanding the risk profile of FMT

1:36:09.600 --> 1:36:12.679
<v Speaker 6>and also the long term curates as well.

1:36:13.280 --> 1:36:18.519
<v Speaker 3>Yes, absolutely, And so you mentioned that this is still

1:36:18.600 --> 1:36:22.320
<v Speaker 3>pretty new and those early studies. When I talk about

1:36:22.360 --> 1:36:25.920
<v Speaker 3>the early studies of FMT, we're talking less than ten

1:36:26.000 --> 1:36:30.360
<v Speaker 3>years ago, and you know, those did show incredible effectiveness

1:36:30.400 --> 1:36:35.880
<v Speaker 3>in curing C. Difficile infection. Has that success been maintained

1:36:36.080 --> 1:36:39.440
<v Speaker 3>since those early studies and as the number of fmts

1:36:39.520 --> 1:36:41.520
<v Speaker 3>performed has increased.

1:36:41.040 --> 1:36:41.920
<v Speaker 4>Over the years.

1:36:42.520 --> 1:36:45.280
<v Speaker 6>Yeah, that's been the really interesting thing. So you know,

1:36:45.400 --> 1:36:50.000
<v Speaker 6>at open Biome we follow the clinical outcomes of each

1:36:50.040 --> 1:36:53.240
<v Speaker 6>patient that receives an FMT. A few years ago, we

1:36:53.320 --> 1:36:56.559
<v Speaker 6>presented data on over two thousand patients who had received

1:36:56.560 --> 1:37:00.280
<v Speaker 6>an open Biome treatment and observed a clinical curate of

1:37:00.400 --> 1:37:04.719
<v Speaker 6>eighty two percent, which is pretty consistent with the findings

1:37:04.720 --> 1:37:08.880
<v Speaker 6>in clinical trials. But also the American College of Gastoroentrology

1:37:08.960 --> 1:37:12.800
<v Speaker 6>or ACG, have been running a patient registry as well

1:37:12.880 --> 1:37:17.479
<v Speaker 6>that I mentioned, and they've to date followed up two

1:37:17.560 --> 1:37:21.240
<v Speaker 6>hundred and fifty nine patients and observed clinical curates of

1:37:21.360 --> 1:37:25.960
<v Speaker 6>ninety percent. And so, you know, we're seeing these findings

1:37:25.960 --> 1:37:30.280
<v Speaker 6>from these randomized control trials being replicated in the real

1:37:30.280 --> 1:37:34.160
<v Speaker 6>world setting, which is very reassuring for the treatment and

1:37:34.240 --> 1:37:38.439
<v Speaker 6>its use in clinical practice. But I think what we

1:37:38.520 --> 1:37:40.920
<v Speaker 6>are going to hopefully learn more about in the coming

1:37:41.000 --> 1:37:44.439
<v Speaker 6>years is how to improve that efficacy, how to select

1:37:44.479 --> 1:37:47.760
<v Speaker 6>patients so that we are using this in the right

1:37:47.800 --> 1:37:54.200
<v Speaker 6>context and the patient's microbiome perhaps is suited to this treatment.

1:37:54.760 --> 1:37:58.439
<v Speaker 6>I think also, you know, simple questions like dosing for example,

1:37:58.840 --> 1:38:01.519
<v Speaker 6>could be potentially optimzed. And so we're still learning so

1:38:01.600 --> 1:38:04.280
<v Speaker 6>much about you know, what it is that leads to

1:38:04.320 --> 1:38:07.520
<v Speaker 6>a clinical cure, why is it that some patients don't respond?

1:38:07.640 --> 1:38:09.559
<v Speaker 6>And you know, hopefully we're going to be gathering more

1:38:09.640 --> 1:38:12.599
<v Speaker 6>data on you know, the real world evidence over time.

1:38:13.439 --> 1:38:13.919
<v Speaker 4>Yeah.

1:38:14.080 --> 1:38:18.840
<v Speaker 3>Yeah, that's that's really interesting. Those are incredibly high cure rates.

1:38:18.880 --> 1:38:21.599
<v Speaker 3>That's it's just an amazing it's just an amazing thing.

1:38:22.720 --> 1:38:28.000
<v Speaker 3>And for this amazing, potentially amazing life saving treatment, there

1:38:28.160 --> 1:38:30.920
<v Speaker 3>have got to be I assume some barriers in terms

1:38:31.000 --> 1:38:35.040
<v Speaker 3>of cost or access. So what are some of those barriers?

1:38:35.760 --> 1:38:38.479
<v Speaker 6>So, yeah, at open Biome, you know, our goal is

1:38:38.520 --> 1:38:42.760
<v Speaker 6>to reduce the costs of treatment so that patients can

1:38:43.360 --> 1:38:47.800
<v Speaker 6>access this at their nearest hospital. And so we've got

1:38:47.800 --> 1:38:50.559
<v Speaker 6>over a thousand hospitals now that are able to provide

1:38:50.600 --> 1:38:53.880
<v Speaker 6>open treatments. And the way that we've reduced the cost

1:38:53.880 --> 1:38:57.080
<v Speaker 6>of treatment is by centralizing all of that. Don't is screening.

1:38:57.520 --> 1:39:00.320
<v Speaker 6>You know, if only three percent of donors pass the

1:39:00.360 --> 1:39:03.799
<v Speaker 6>clinical screening, you can imagine that a ninety seven percent

1:39:03.840 --> 1:39:06.880
<v Speaker 6>of that for a clinician to be able to screen

1:39:06.920 --> 1:39:09.880
<v Speaker 6>donors who may not be eligible is really extensive. And

1:39:09.920 --> 1:39:12.400
<v Speaker 6>so you know if for a clinician to do this

1:39:12.520 --> 1:39:16.759
<v Speaker 6>themselves can range from four thousand to up to twenty

1:39:16.840 --> 1:39:22.040
<v Speaker 6>thousand dollars per single treatment in an open by and

1:39:22.400 --> 1:39:25.480
<v Speaker 6>we charged just over two thousand dollars for our treatments,

1:39:26.040 --> 1:39:29.360
<v Speaker 6>and so that hopefully makes the treatment itself more accessible.

1:39:29.960 --> 1:39:34.559
<v Speaker 6>But FMT today is still an investigational drug, so it

1:39:34.600 --> 1:39:38.679
<v Speaker 6>hasn't received an approval from the FDA. It's being provided

1:39:38.720 --> 1:39:42.960
<v Speaker 6>to patients under a framework called enforcement discretion. What does

1:39:42.960 --> 1:39:45.880
<v Speaker 6>that mean to this question? It means that the treatment

1:39:45.960 --> 1:39:48.640
<v Speaker 6>itself at the moment isn't covered by insurance, and so

1:39:49.240 --> 1:39:52.000
<v Speaker 6>patients are having to pay out of pocket for it

1:39:52.760 --> 1:39:55.479
<v Speaker 6>or altensively. You know, the clinicians are having to eat

1:39:55.560 --> 1:39:58.760
<v Speaker 6>up the cost themselves, and so that obviously creates a

1:39:58.800 --> 1:40:01.679
<v Speaker 6>barrier to access as especially if we're thinking about coverage

1:40:01.720 --> 1:40:04.519
<v Speaker 6>in some of the more rural areas or centers that

1:40:04.960 --> 1:40:09.040
<v Speaker 6>might not be near a large gastrotrologists or infectious disease practice.

1:40:09.680 --> 1:40:13.160
<v Speaker 6>But you know, I think an interesting other lens on

1:40:13.240 --> 1:40:16.479
<v Speaker 6>this is that, given we are still quite early in

1:40:16.520 --> 1:40:21.200
<v Speaker 6>the field, is there some justification for potentially building up

1:40:21.240 --> 1:40:24.599
<v Speaker 6>centers of excellence that can provide this treatment At their

1:40:24.640 --> 1:40:28.599
<v Speaker 6>centers do all of the really sort of rigorous screening

1:40:28.600 --> 1:40:32.559
<v Speaker 6>and assessment of the patient and follow up and really

1:40:32.720 --> 1:40:36.160
<v Speaker 6>you know, gathering the data to understand how effective this

1:40:36.200 --> 1:40:36.800
<v Speaker 6>treatment is.

1:40:38.160 --> 1:40:42.839
<v Speaker 3>Right, Yeah, So in this episode so far, we've largely

1:40:42.880 --> 1:40:47.960
<v Speaker 3>been focusing on fmts in the context of clostridium deficile,

1:40:48.560 --> 1:40:51.439
<v Speaker 3>but they have been found to be an effective treatment

1:40:51.520 --> 1:40:53.880
<v Speaker 3>for a number of other conditions, or at least there's

1:40:53.920 --> 1:40:58.520
<v Speaker 3>been early explorative research looking at fmts for other conditions.

1:40:59.080 --> 1:41:01.559
<v Speaker 3>So can you take us through some of the research

1:41:01.640 --> 1:41:04.439
<v Speaker 3>that open Biome is working on in terms of other

1:41:04.479 --> 1:41:07.800
<v Speaker 3>applications of FMT beyond ce diff infections.

1:41:08.439 --> 1:41:12.360
<v Speaker 6>Yeah, sure thing. So I think one example that's really

1:41:12.360 --> 1:41:15.840
<v Speaker 6>interesting and potentially points us to how the field might

1:41:15.880 --> 1:41:20.160
<v Speaker 6>move in the future is a clinical trial that we

1:41:20.280 --> 1:41:25.240
<v Speaker 6>did looking at fecal transplants in hepatica and caphilopathy. So,

1:41:25.360 --> 1:41:30.200
<v Speaker 6>hepatica cathelopathy is a condition that is associated with late

1:41:30.200 --> 1:41:35.160
<v Speaker 6>stage liver disease liver cirrhosis, and it is characterized by

1:41:35.240 --> 1:41:40.519
<v Speaker 6>confusion and agitation, drowsiness, loss of consciousness, and can be

1:41:40.600 --> 1:41:44.160
<v Speaker 6>you know, putting patients into the intensive care unit and

1:41:44.320 --> 1:41:47.519
<v Speaker 6>is typically quite a challenging condition to treat, especially to

1:41:47.680 --> 1:41:52.280
<v Speaker 6>maintain clinical cure. But it's caused by a build up

1:41:52.320 --> 1:41:55.640
<v Speaker 6>of nitrogenous waste products that you know, accumulating the systemic

1:41:55.840 --> 1:41:59.200
<v Speaker 6>circulation and part of the role of the gut bacterias

1:41:59.240 --> 1:42:02.280
<v Speaker 6>to break down some of those waste products. And so,

1:42:02.360 --> 1:42:05.960
<v Speaker 6>working with a colleague of others, doctor Chaz Bagage at

1:42:06.520 --> 1:42:10.880
<v Speaker 6>University of Virginia, we conducted a randomized control trial that

1:42:11.120 --> 1:42:16.960
<v Speaker 6>showed that FMT was able to effectively treat this Basically

1:42:16.960 --> 1:42:19.360
<v Speaker 6>in this trial of about twenty vations so a small study,

1:42:19.680 --> 1:42:22.599
<v Speaker 6>half of the patients in standard of care group were

1:42:22.640 --> 1:42:25.360
<v Speaker 6>cured and all of the patients in the FMT arm

1:42:25.640 --> 1:42:28.599
<v Speaker 6>had a clinical cure. And so that's just a really

1:42:28.600 --> 1:42:31.479
<v Speaker 6>interesting sort of example of you know, we talk about

1:42:31.520 --> 1:42:33.800
<v Speaker 6>the gut brain axis, and you know, this is sort

1:42:33.840 --> 1:42:37.360
<v Speaker 6>of an early example of how potentially FMT and the

1:42:37.360 --> 1:42:39.840
<v Speaker 6>gut microbiome may play a role in that. The other

1:42:39.880 --> 1:42:41.719
<v Speaker 6>piece of the study that I think is really interesting

1:42:41.880 --> 1:42:45.200
<v Speaker 6>is doctor Bajaj characterized the gut microbiomes of these patients

1:42:45.560 --> 1:42:48.439
<v Speaker 6>before the study to see whether there were some common

1:42:48.560 --> 1:42:52.840
<v Speaker 6>microbial signatures in the composition or function of the microbiomes

1:42:52.840 --> 1:42:56.080
<v Speaker 6>and these patients. And you know, we observed that these

1:42:56.080 --> 1:43:00.639
<v Speaker 6>patients were particularly depleted in bacteria that play a role

1:43:00.720 --> 1:43:03.000
<v Speaker 6>in the production of short chain fatty acids. And so

1:43:03.680 --> 1:43:05.959
<v Speaker 6>what we did was to go back to our donors

1:43:06.280 --> 1:43:09.680
<v Speaker 6>and we characterized the microbians of our donors and selected

1:43:09.720 --> 1:43:14.160
<v Speaker 6>a donor that had a particularly high abundance of these

1:43:14.200 --> 1:43:18.120
<v Speaker 6>microbes that these patients were depleted in. And so, you know,

1:43:18.160 --> 1:43:22.000
<v Speaker 6>that sort of rational donor selection or personalized medicine approach

1:43:22.080 --> 1:43:24.479
<v Speaker 6>to this maybe something that we see more and more

1:43:24.479 --> 1:43:27.599
<v Speaker 6>in the future. And you know with the sort of

1:43:27.840 --> 1:43:31.240
<v Speaker 6>falling costs of genomics and the introduction of that into

1:43:31.280 --> 1:43:34.120
<v Speaker 6>clinical practice, So I think that's a really interesting one.

1:43:34.280 --> 1:43:37.200
<v Speaker 6>You know, the other diseases like inflammatory bowel disease, there've

1:43:37.200 --> 1:43:39.519
<v Speaker 6>been a number of trials now that have shown promise

1:43:39.560 --> 1:43:43.120
<v Speaker 6>in that, especially in alternative colitis, where you know, we're

1:43:43.160 --> 1:43:48.559
<v Speaker 6>seeing in patients with this very difficult disease about thirty

1:43:48.600 --> 1:43:52.280
<v Speaker 6>seven percent of patients are in clinical remission after a FMT,

1:43:52.439 --> 1:43:55.639
<v Speaker 6>which compared to about eighteen to twenty percent for standard

1:43:55.640 --> 1:43:59.200
<v Speaker 6>of care. Is really exciting. And then you know, as

1:43:59.200 --> 1:44:03.320
<v Speaker 6>a nonprofit, we are also exploring the role of this

1:44:03.439 --> 1:44:08.480
<v Speaker 6>in disease areas that are perhaps neglected by farmer companies

1:44:08.720 --> 1:44:11.640
<v Speaker 6>in the US and Europe, to support clinical trials in

1:44:12.280 --> 1:44:14.880
<v Speaker 6>lonand Lincoln Countries, and so we're actually working with the

1:44:14.920 --> 1:44:17.439
<v Speaker 6>University of Kicktown at the moment looking at the role

1:44:17.479 --> 1:44:21.280
<v Speaker 6>of fecal transplant in children with severe cute malnutrition who

1:44:21.360 --> 1:44:26.440
<v Speaker 6>failed to respond to a nutritional therapy, which is surprisingly

1:44:26.640 --> 1:44:28.840
<v Speaker 6>the case in about a third of kids with malnutrition.

1:44:29.680 --> 1:44:33.720
<v Speaker 6>So yeah, really broad disease areas that we're working on.

1:44:33.800 --> 1:44:37.960
<v Speaker 3>So that is so incredible though, that is I mean, yeah,

1:44:38.080 --> 1:44:42.479
<v Speaker 3>like you said, very broad but promising, and it's just

1:44:42.560 --> 1:44:46.760
<v Speaker 3>seems like such an incredible potential solution. So what do

1:44:46.800 --> 1:44:50.120
<v Speaker 3>you see as the future of FMT. What hopes do

1:44:50.200 --> 1:44:52.479
<v Speaker 3>you have for FMT in the future.

1:44:53.120 --> 1:44:56.280
<v Speaker 6>Yeah, so, I think we are at such an early

1:44:56.360 --> 1:45:01.040
<v Speaker 6>stage of our understanding of the microbiome and the potential

1:45:01.479 --> 1:45:04.760
<v Speaker 6>and the way that we should be using FMT, And

1:45:05.160 --> 1:45:08.080
<v Speaker 6>what I hope is a few things. I think firstly,

1:45:09.080 --> 1:45:13.720
<v Speaker 6>that we've accumulated more and more data on patient outcomes

1:45:14.080 --> 1:45:17.519
<v Speaker 6>in a more systematic way across the world for all

1:45:17.560 --> 1:45:20.360
<v Speaker 6>patients that are receiving this treatment. I think the second

1:45:20.560 --> 1:45:25.599
<v Speaker 6>pieces that aspect of personalization, and you know, can we

1:45:25.800 --> 1:45:30.720
<v Speaker 6>do more to potentially increase the curates for patients who

1:45:30.720 --> 1:45:34.800
<v Speaker 6>are receiving FMT for conditions like cediff And you know,

1:45:35.240 --> 1:45:38.920
<v Speaker 6>perhaps in the future, you know, we're treating patients who

1:45:39.000 --> 1:45:42.920
<v Speaker 6>have failed multiple rounds of antibiotics, But is there potentially

1:45:42.960 --> 1:45:45.799
<v Speaker 6>more that we can do in prevention. Is there a world,

1:45:46.080 --> 1:45:48.120
<v Speaker 6>you know, perhaps you know in a few years time

1:45:48.760 --> 1:45:52.800
<v Speaker 6>where you bank your stool prior to receiving antibiotics and

1:45:52.880 --> 1:45:57.040
<v Speaker 6>then you receive your own stool back to restore your

1:45:57.040 --> 1:46:01.040
<v Speaker 6>gut microbiome after a course of antibiotics. This is already

1:46:01.040 --> 1:46:05.160
<v Speaker 6>being explored in some patients, some patient populations who are

1:46:06.320 --> 1:46:09.200
<v Speaker 6>receiving lots of antibiotics, like stem cell transplant patients. But

1:46:09.880 --> 1:46:13.960
<v Speaker 6>we I think open Biome are really interested in a

1:46:13.960 --> 1:46:17.400
<v Speaker 6>public health approach to FMT in the microbiome, and can

1:46:17.439 --> 1:46:20.400
<v Speaker 6>we prevent diseases as much as treating them when patients

1:46:20.400 --> 1:46:23.439
<v Speaker 6>are really sick? And you know, i'd say sort of.

1:46:23.439 --> 1:46:26.760
<v Speaker 6>The last thing really is we started open Biome to

1:46:27.040 --> 1:46:30.160
<v Speaker 6>enable access to this treatment for patients when they need it.

1:46:30.680 --> 1:46:32.840
<v Speaker 6>We know that there's still much more to do for

1:46:32.960 --> 1:46:37.040
<v Speaker 6>that in the US, but I think globally, SEEDIFF is

1:46:37.560 --> 1:46:40.559
<v Speaker 6>likely to become more and more of a burden as

1:46:40.680 --> 1:46:45.720
<v Speaker 6>we see wider antibiotic use and wider occurrence of risk

1:46:45.760 --> 1:46:48.920
<v Speaker 6>factors they are associated with seed IFF, like inflammatory bowel disease,

1:46:49.400 --> 1:46:50.840
<v Speaker 6>And so I think we're going to have to be

1:46:50.960 --> 1:46:54.200
<v Speaker 6>really mindful of making sure that people who may not

1:46:54.320 --> 1:46:56.640
<v Speaker 6>necessarily have access to the same health systems as we

1:46:56.680 --> 1:46:59.680
<v Speaker 6>do in the US can still access this treatment when

1:46:59.720 --> 1:47:02.680
<v Speaker 6>they need it. I think COVID has highlighted more than

1:47:02.680 --> 1:47:06.080
<v Speaker 6>ever the importance of sort of health equity and technologies

1:47:06.080 --> 1:47:08.800
<v Speaker 6>and access to them as quickly as possible, and so

1:47:08.840 --> 1:47:11.799
<v Speaker 6>I think, yeah, hopefully that's the other piece that gets

1:47:12.160 --> 1:47:14.479
<v Speaker 6>resolved and we're all working towards over time.

1:47:38.760 --> 1:47:44.320
<v Speaker 3>Thank you so much, doctor Osmond. That was just so

1:47:44.520 --> 1:47:47.640
<v Speaker 3>enlightening and I think I somehow I didn't know it

1:47:47.760 --> 1:47:51.120
<v Speaker 3>was possible love fecal microbida transplants that much.

1:47:51.000 --> 1:47:53.880
<v Speaker 2>More, even more, even more, Oh, Aeron, what a fun

1:47:53.880 --> 1:47:54.760
<v Speaker 2>episode this was.

1:47:55.360 --> 1:47:57.599
<v Speaker 3>This was very interesting. I mean it did have its

1:47:57.600 --> 1:48:01.559
<v Speaker 3>frustrating moments. Yeah, like I.

1:48:01.439 --> 1:48:05.760
<v Speaker 2>Really wish that we had better numbers, and yeah, there's

1:48:05.760 --> 1:48:09.120
<v Speaker 2>a lot of frustrations.

1:48:07.040 --> 1:48:10.640
<v Speaker 3>But this was I mean, I think sea diiff is

1:48:11.560 --> 1:48:16.720
<v Speaker 3>a very remarkable pathogen, and that it's not necessarily a pathogen,

1:48:17.280 --> 1:48:21.360
<v Speaker 3>and its recent emergence and how much our existing medical

1:48:21.439 --> 1:48:25.600
<v Speaker 3>structures kind of facilitate the growth of this bacterium and

1:48:25.640 --> 1:48:29.040
<v Speaker 3>the spread of it is terrifying.

1:48:29.680 --> 1:48:30.320
<v Speaker 4>Absolutely.

1:48:31.080 --> 1:48:38.160
<v Speaker 3>Yeah. Well, okay, should we do sources? Yeah, let's okay.

1:48:38.960 --> 1:48:40.400
<v Speaker 3>So I'm just going to shout out a few. I

1:48:40.439 --> 1:48:43.000
<v Speaker 3>have a bunch of papers, but a couple that were

1:48:43.120 --> 1:48:47.280
<v Speaker 3>key for the history and genomic aspects of sea diff.

1:48:47.800 --> 1:48:51.000
<v Speaker 3>One is by Bartlett from two thousand and eight. And

1:48:51.040 --> 1:48:53.160
<v Speaker 3>the other is the one that I already mentioned by

1:48:53.280 --> 1:48:56.200
<v Speaker 3>night at All from twenty fifteen. And then in terms

1:48:56.280 --> 1:49:00.280
<v Speaker 3>of the fecal microbide of transplant stuff, I contain multitudos

1:49:00.280 --> 1:49:03.480
<v Speaker 3>by Edyong, a very fun book about the human microbiome.

1:49:03.560 --> 1:49:06.120
<v Speaker 3>Check it out, and by de Groot at All from

1:49:06.120 --> 1:49:09.559
<v Speaker 3>twenty seventeen. And I have to shout this out also

1:49:09.800 --> 1:49:12.840
<v Speaker 3>because it doesn't just have great information, but it also

1:49:12.880 --> 1:49:16.840
<v Speaker 3>contains and amazing figure. One of my favorite that I've

1:49:16.840 --> 1:49:20.559
<v Speaker 3>seen of the most important developments in the timeline of

1:49:20.560 --> 1:49:26.160
<v Speaker 3>fecal microbida transplants, but it's marked along intestines. It's starting

1:49:26.200 --> 1:49:28.600
<v Speaker 3>in one part of the intestine going together. It's beautiful.

1:49:28.640 --> 1:49:29.639
<v Speaker 4>Oh that's so cool.

1:49:29.960 --> 1:49:30.519
<v Speaker 3>I loved it.

1:49:31.640 --> 1:49:33.080
<v Speaker 4>Yeah.

1:49:33.120 --> 1:49:36.360
<v Speaker 2>One of my favorite papers that I read was actually

1:49:37.240 --> 1:49:41.760
<v Speaker 2>it was by crowboch at All twenty eighteen called Understanding

1:49:42.000 --> 1:49:46.360
<v Speaker 2>Clusterdium difficile Colonization. I found that one just really really interesting.

1:49:46.760 --> 1:49:49.360
<v Speaker 2>But there was a number of other review papers on

1:49:49.880 --> 1:49:56.040
<v Speaker 2>sort of seediff infection and a couple at least including

1:49:56.400 --> 1:50:00.479
<v Speaker 2>the Global Burden of Clusterdium difficile Infections, A system review

1:50:00.520 --> 1:50:03.639
<v Speaker 2>and meta analysis that we're trying to get at the

1:50:03.680 --> 1:50:08.200
<v Speaker 2>global distribution. Yeah, so we'll post a list of all

1:50:08.240 --> 1:50:10.439
<v Speaker 2>of those sources on our website, This podcast will Kill

1:50:10.479 --> 1:50:12.679
<v Speaker 2>You dot Com under the episodes tab.

1:50:13.439 --> 1:50:17.080
<v Speaker 3>Thanks again, Lany so much for providing the first hand account.

1:50:17.400 --> 1:50:20.360
<v Speaker 3>We really appreciate you taking the time to chat with us.

1:50:20.800 --> 1:50:21.479
<v Speaker 4>Yeah, thank you.

1:50:22.280 --> 1:50:25.120
<v Speaker 2>Thank you also to Bloodmobile, who provides the music for

1:50:25.200 --> 1:50:27.320
<v Speaker 2>this episode and all of our episodes.

1:50:27.840 --> 1:50:30.559
<v Speaker 3>And thank you to exactly Right, of whom we are

1:50:30.600 --> 1:50:32.120
<v Speaker 3>a very proud part.

1:50:34.040 --> 1:50:35.920
<v Speaker 4>And thank you to you listeners.

1:50:36.400 --> 1:50:40.040
<v Speaker 2>You make this podcast possible and we love you for it,

1:50:40.520 --> 1:50:41.240
<v Speaker 2>we really do.

1:50:42.120 --> 1:50:47.240
<v Speaker 3>Especially thanks also to our patrons. You guys are absolutely amazing.

1:50:48.040 --> 1:50:52.320
<v Speaker 3>We love you, we appreciate you. It's just incredible, a

1:50:52.479 --> 1:50:58.960
<v Speaker 3>joy it is. Okay, well, this feels quite relevant, but

1:50:59.160 --> 1:51:03.400
<v Speaker 3>does until next time, wash your hands.

1:51:03.280 --> 1:51:06.080
<v Speaker 2>You filthy animals, with soap and water and not just

1:51:06.120 --> 1:51:07.880
<v Speaker 2>an alcohol based hand sanitizer.

1:51:10.560 --> 1:51:11.040
<v Speaker 4>I like that.