Speaker 1: Hi, I'm Laney. So in August of twenty nineteen, I
Speaker 1: started having wild bowel movements. That's about the only way
Speaker 1: that I can put it. I have celiac. I have
Speaker 1: irritable bowel. And these stools were nothing like I had
Speaker 1: ever encountered before. They were coming every hour to half
Speaker 1: an hour. Seemed like I couldn't be more than ten
Speaker 1: feet from my bathroom at any given time. I went
Speaker 1: to our little local first daid station kind of at
Speaker 1: my husband's job, and they had medical staff, and I said, look,
Speaker 1: something's not right, it's not okay. I intentionally withheld the
Speaker 1: fact that I had celiac disease, knowing that a lot
Speaker 1: of doctors actually like to just hang their hat on
Speaker 1: any GI symptom. And at the very end she had
Speaker 1: had gone through everything was gonna just basically say, if
Speaker 1: it's still not okay in a couple of days, come back.
Speaker 1: And somehow the word got out that I had celiac disease.
Speaker 1: And she said, oh, you must have just had gluten,
Speaker 1: that's all. And even though I was sure, she said,
Speaker 1: have some bananas, drink lots of water. Your stool should
Speaker 1: firm up and everything will be fine, and all I
Speaker 1: really wanted to do was go to my normal GP,
Speaker 1: but in rural Iowa, he was over an hour away
Speaker 1: and I could not make that trip to save my life.
Speaker 1: No bathrooms on the way, no gas stations. It would
Speaker 1: have been like me in a cornfield, So not an option. Finally,
Speaker 1: when I was having what I would consider a good day,
Speaker 1: I called my doctor and I said, I'm on my way,
Speaker 1: I need to come see you, and he submitted a
Speaker 1: test for SEDIFF. Sure enough, I came back positive. From there,
Speaker 1: we went through basically the standard first steps and I
Speaker 1: was put on a course of metronitisolar flagile. I saw
Speaker 1: a little improvement, but once the course of antibiotics was finished,
Speaker 1: it was all right back. So then he called in
Speaker 1: oral Vancomyasin. Thankfully that cleared it up. After the fact,
Speaker 1: we were trying to do a little research on how
Speaker 1: I acquired my seat of infection, and it wasn't until
Speaker 1: it was a long thought, afterthought that I had a
Speaker 1: bug bite before that and it had gotten infected and
Speaker 1: they had put me on superflexis in about two months prior.
Speaker 1: Fast forwarding to March of twenty twenty one, I am
Speaker 1: a vet tech and it was my third week on
Speaker 1: the job, we were still doing curbside because of COVID.
Speaker 1: I went out to go get a dog to bring
Speaker 1: it into the hospital. Somehow the dogs muscle slipped off
Speaker 1: when the owner was placing its lead on it, lunched
Speaker 1: at me, tackled me into a snow bank, and I
Speaker 1: had puncture wounds in my arm and had to go
Speaker 1: seek medical attention, where they put me on clintamyasin and zyperflexisin.
Speaker 1: I mentioned to urgent care, I have a history of cediff.
Speaker 1: Please help me. That's not what we should be doing.
Speaker 1: And instead of her directions for having a yogurt every day,
Speaker 1: she suggested a take to have two yogurts every day.
Speaker 1: That was a little insulting, to say the least. A
Speaker 1: few days later, my armhead absessed. I went to my
Speaker 1: current doctor's emergency room. I went in and they said,
Speaker 1: we need to admit you to the hospital. They started
Speaker 1: me on ivy vankamyasin, ivy metronitisol and ivy is trianam,
Speaker 1: which is a pretty kind of novel antibiotic that they
Speaker 1: only use in real serious cases. From there, my bite
Speaker 1: moom cleaned up. I was messaging my doctor like every day,
Speaker 1: at least a couple times a day, freaking out about
Speaker 1: having sea diiff again, sure that I was probably going
Speaker 1: to have it again, and he agreed that I was
Speaker 1: probably going to have seediff again from all of these antibiotics. Finally,
Speaker 1: when I was discharged from the hospital three days later,
Speaker 1: they don't have an oral version of as tree and am,
Speaker 1: so they put me on leva floxis, in another broad
Speaker 1: spectrum antibiotic. My heart kind of sank, knowing what the
Speaker 1: future held. It was about ten days after I was
Speaker 1: home from the hospital, had gone back to work, those
Speaker 1: urgent loose tools that when you feel it you need
Speaker 1: to sprint to the bathroom, but don't spread too fast.
Speaker 1: And I called my doctor and I said, look, I
Speaker 1: think I've got sea diiff. He ordered the test. I
Speaker 1: came down and I positive for SEEDFF. So they started
Speaker 1: me on oral vank commiasin right away, and finally, after
Speaker 1: it was a month on the bank commosin and doing
Speaker 1: a taper, things were starting to kind of finally feel normal.
Speaker 1: I finished my antibiotics and it wasn't three days later
Speaker 1: before I was at work and I realized, in the
Speaker 1: last hour and a half I've gone to the bathroom
Speaker 1: three times. I messaged my doctor while I was at work.
Speaker 1: I said, I need another test. I don't think it's gone,
Speaker 1: And sure enough I went over our lunch break, I
Speaker 1: took a longer lunch than we normally have and went
Speaker 1: down and by the time we were done. That night
Speaker 1: at work, I had my results that I had seediff again.
Speaker 1: I had a recurren seed if infection. That meant my
Speaker 1: doctor was calling infectious disease specialists and I spoke to
Speaker 1: infectious disease specialists and they referred me immediately to you
Speaker 1: a research trial for fecal transplant. They didn't even want
Speaker 1: to see me and they just sent me straight there.
Speaker 1: Then I get the phone call and I tell them
Speaker 1: my story. They said, you absolutely qualify for a fecal
Speaker 1: transplant with your recurrent infection. Will schedule you for. It
Speaker 1: was June thirtieth. It was my transplant date, and I
Speaker 1: had it circled and like starred on a calendar, but
Speaker 1: it was still a month out. So it was exhilarating
Speaker 1: but also a nerving knowing that I had to deal
Speaker 1: with this infection. So we started another Vincimizon taper. I
Speaker 1: stayed on the dose that basically kept my stools solid.
Speaker 1: From there, I waited until my transplant date. My transplant
Speaker 1: was colon ascapy guided, so they did a colonoscopy and
Speaker 1: then they came in and applied the fecal transplant matter.
Speaker 1: I remember wheeling it in to the colon ass could
Speaker 1: be room and seeing a jar with brown liquid in it,
Speaker 1: and I took a selfie with it. I was so excited.
Speaker 1: I screamed, that's my poop, that's my new poop, and
Speaker 1: the doctors laughed at me. I was just so excited. Thankfully,
Speaker 1: post transplant, things are going well. I have post infectious
Speaker 1: irritable bewel, probably on top of normal irritable bell, but
Speaker 1: they're still calling it post infection. So day to day
Speaker 1: life things are going pretty well. However, every time I
Speaker 1: feel like a little gas bubble or I get a
Speaker 1: funny little cramp, my heart sinks and I'm worried that
Speaker 1: the seed off his back because the doctors did notify
Speaker 1: me that my infection was relatively severe and that I
Speaker 1: might have to kind of get what they call little
Speaker 1: tune ups as far as just additional fecal transplants in
Speaker 1: the future, and so every time I get a funny
Speaker 1: little feeling I'm instantly worried, and my doctor even associates
Speaker 1: that with a little bit of PTSD. Honestly, from the
Speaker 1: whole event, it's interesting to think that I have more
Speaker 1: trauma from the medical fallout from my dog bite than
Speaker 1: the actual dog bite itself. Seed Iff has really stuck
Speaker 1: with me for anyone who's comparing it, because my mom
Speaker 1: was trying to put a label on it. She was saying,
Speaker 1: it can't be worse than kolonoscopy prep. It can't be
Speaker 1: worse than kolonoscopy prep. And I can officially say, after
Speaker 1: doing both that seed Iff is much worse.
Speaker 2: Wow.
Speaker 3: Thank you so much, Laney for taking the time to
Speaker 3: share your story with us. That's intense.
Speaker 4: Yeah, wow, thank you.
Speaker 1: Hi.
Speaker 3: I'm Erin Welsh and I'm Erin Alman Updike and this
Speaker 3: is this podcast will kill you.
Speaker 2: Welcome everyone.
Speaker 4: We're excited about this episode.
Speaker 3: As we are about all our episodes. It's genuine excitement.
Speaker 4: It always is.
Speaker 2: Today we're talking about Claustridium difficile a ka se diff Seediff.
Speaker 3: That's how I'm going to talk about it for the
Speaker 3: of the episode. But we're not talking just about this
Speaker 3: problematic pathogen. We're also talking about one of my favorite
Speaker 3: solutions to infection.
Speaker 2: Yeah, one of my favorite solutions to a problem.
Speaker 3: Yeah, yeah, I simply love it. And of course we
Speaker 3: are talking about fecal microbiota transplantation.
Speaker 2: Aka fecal transplant. We have talked about this like, we've
Speaker 2: dabbled in it and several other episodes and been like ooh, someday, ooh, someday,
Speaker 2: that day.
Speaker 4: Is finally here everyone.
Speaker 3: Yes, this is not going to be like a full
Speaker 3: takedown of the microbiome and all the impact that it
Speaker 3: has on different conditions or whatever in this associations, but
Speaker 3: we are going to do somewhat of a deep dive
Speaker 3: into fecal transplants or fmts, and we are very excited
Speaker 3: to bring on a special guest, an expert guest, to
Speaker 3: help us out with that. But that's jumping way ahead
Speaker 3: of ourselves.
Speaker 2: It is because first, it's quarantine.
Speaker 3: Any time, it is what are we drinking this week?
Speaker 2: This week we're drinking the slurry?
Speaker 3: This We're sorry is that when everyone wants to drink? Okay,
Speaker 3: So the thing is, it was either make a gross
Speaker 3: recipe or a gross name and not both and so
Speaker 3: one or the other had to happen. But yeah, exactly,
Speaker 3: I mean, like we are but human. So what is
Speaker 3: in the slurry? This?
Speaker 2: The slurry contains mango, pineapple, lime, tamarind, and tequila, all
Speaker 2: delicious things. And of course you gotta blend it up.
Speaker 3: You got to. You gotta blend it up. But it
Speaker 3: tastes good, right, and it's like yeah, so.
Speaker 2: I mean, it's like very fruity. It's a lot of flavors.
Speaker 2: We promise it's worth it.
Speaker 3: Yeah, yeah, And we will post the full recipe for
Speaker 3: this slurry quarantine as well as the non alcoholic place
Speaker 3: sy Burrita on our website this podcast will Kill You
Speaker 3: dot com, as well as on all of our social
Speaker 3: media channels.
Speaker 2: Yes, we will, Aaron, What other business should we tell
Speaker 2: everyone about?
Speaker 3: Well, how about our website? Okay, it's my turn to
Speaker 3: do the rundown of things on there. I'm nervous.
Speaker 4: You can do it. I believe in you.
Speaker 3: Okay, here we go. We have all of our references
Speaker 3: to all of our episodes on each episode page. We
Speaker 3: have transcripts. We have links to our bookshop dot org
Speaker 3: affiliate page, and our good Raids list. We have links
Speaker 3: to music Bloodmobile now on Spotify. We have links to
Speaker 3: our merch which we have very incredible merch.
Speaker 4: Please check it out.
Speaker 3: And we have a pro code page. I mean, I
Speaker 3: think that's that's got to be most of the things
Speaker 3: on there.
Speaker 2: It's most of the things. Definitely check it out. This
Speaker 2: podcast will kill You dot com. So does that mean
Speaker 2: we're ready to talk about C DIFF?
Speaker 1: Yeah?
Speaker 3: I think I think so. Thanks also to everyone who
Speaker 3: has requested this over the years. Yeah, and we hope
Speaker 3: you liked the episode.
Speaker 2: Yeah, so let's get right into it after this break.
Speaker 1: So.
Speaker 2: I don't know if anyone but me would notice this,
Speaker 2: but I think it's funny. I'm going to start this
Speaker 2: episode almost identically to Anthrax. I think, oh our Anthrax episode.
Speaker 3: I don't remember this, so this is good.
Speaker 2: It's fine, nobody will. But as I was typing it,
Speaker 2: I was like, this sounds familiar. And then I opened
Speaker 2: my Anthrax notes and I was like, ah, okay. Claustridium
Speaker 2: difficile infection is caused by an anaerobic gram positive rod
Speaker 2: shaped spore forming toxin producing bacterium.
Speaker 4: Yeah.
Speaker 3: Hold on, okay, a quick question already already?
Speaker 4: What then is that? Also?
Speaker 3: How you started the botulism episode.
Speaker 2: Ooh, probably, yeah, probably, Okay, I genuinely forgot that we
Speaker 2: ever did botulism erin.
Speaker 4: It was a long time ago.
Speaker 3: I loved that. I loved that it was.
Speaker 4: A good episode. I forgot.
Speaker 2: It'll also be probably the way that I start tetanus
Speaker 2: whenever we do that, so, you know, So for the
Speaker 2: remainder of this episode, like we said, I'm probably just
Speaker 2: gonna refer to this as sea diff because it's easier
Speaker 2: and shorter, and that's how I'm we're gonna say it. So,
Speaker 2: sea diff causes an infection that most of the time,
Speaker 2: very commonly is what's called a nosocomial infection, which means
Speaker 2: hospital or healthcare acquired. So the way that I've tried
Speaker 2: to organize this biology section is to first focus on
Speaker 2: the disease that Clusterdium difficiale can cause, how it's transmitted,
Speaker 2: how it makes us sick, and then take kind of
Speaker 2: a bigger picture view and talk a little bit about
Speaker 2: the microbiome as it relates to sea diff infection.
Speaker 4: Because as a spoiler.
Speaker 2: That Aaron, I know, you probably already know, and many
Speaker 2: listeners may know, but se diff doesn't always or necessarily
Speaker 2: cause infection.
Speaker 3: Yeah, it's it's like, uh, it's got to be one
Speaker 3: of our first besides MRSA maybe like opportunistic super opportunistic pathogens.
Speaker 2: Yeah, we haven't covered a lot of opportunistic pathogens on here.
Speaker 2: This is definitely one of them, but we'll get there eventually.
Speaker 2: First of all, transmission of sea diff at like the
Speaker 2: most basic level. The way that anyone in the world
Speaker 2: gets exposed to sea diff in the first place is
Speaker 2: fecal oral so poop in mouth. It's a common mode
Speaker 2: of transmission, especially for GI bacteria, and sea diff, like
Speaker 2: I mentioned, is a spore forming bacterium like our friend
Speaker 2: Bascillas anthrasis and Clusterdium tetani and also Botulinum and clusterdrium bochculainum. Anyways,
Speaker 2: see diff is also an anaerobic bacterium. Like a lot
Speaker 2: of our gut bacteria are either entirely or facultatively anaerobic,
Speaker 2: which means that they survive without oxygen. So what happens
Speaker 2: in the case of seedff is that on contact with oxygen,
Speaker 2: like when we poop out this bacterium, it forms spores,
Speaker 2: and these spores are very highly environmentally resistant inactive forms
Speaker 2: of this bacteria. They really can't easily be killed by
Speaker 2: heat or cold or alcohol, and they can persist in
Speaker 2: the environment, not dying or desiccating, just hanging out until
Speaker 2: they're ingested by another human or animal, because animals can
Speaker 2: also get infected.
Speaker 4: And then once we ingest them.
Speaker 2: These spores can easily survive the acidic environment of our stomach,
Speaker 2: travel through our guts, and then these spores are activated
Speaker 2: in our small or large intestine when they come into
Speaker 2: contact with our bile acids.
Speaker 4: Hmm, isn't that fascinating?
Speaker 3: Yeah, okay, I have a question about how long these
Speaker 3: spores can last.
Speaker 4: Oh, good question.
Speaker 2: I don't have an exact timeline, but definitely on the
Speaker 2: order of months, possibly years, depending on the conditions.
Speaker 3: I really hate that about these things. Yeah, it's very
Speaker 3: It makes it very scary and like it feels a
Speaker 3: bit challenging.
Speaker 4: Oh, very very challenging.
Speaker 1: Huh.
Speaker 3: Okay, So the bile acids, like, what about them?
Speaker 5: Yeah?
Speaker 3: What is bile acid I'm.
Speaker 4: So glad that you asked, Arin.
Speaker 2: Let me tell you so. Bile acids are basically cholesterol derivatives.
Speaker 2: Our liver makes bile and secretes it into our gallbladder
Speaker 2: where it's like stored, and then whenever you eat something,
Speaker 2: it sends signals to our gall butter to contract squeeze
Speaker 2: out the bile and that goes into our small intestine.
Speaker 2: And these bile acids help support digestion, especially the digestion
Speaker 2: and eventual absorption.
Speaker 3: Of fats huh okay.
Speaker 2: And it's a little bit more complicated. There's like multiple
Speaker 2: kinds of bile acids, and they're converted in our small
Speaker 2: intestine from like primary into secondary. And it seems like
Speaker 2: when sea diff spores come into contact with some types
Speaker 2: of these bio acids, especially in higher concentrations, that's when
Speaker 2: they very easily reactivate into a live, replicatable, mobile sea
Speaker 2: diff bacteria, which can then replicate and replicate and kind
Speaker 2: of beat out other bacteria in our guts and eventually
Speaker 2: cause infection.
Speaker 3: Are there other bacteria that are activated or inactivated by
Speaker 3: biole like do the bile acids kill a lot of
Speaker 3: potentially food born bacteria or are other food born bacteria
Speaker 3: resistant to bio acids.
Speaker 2: That's a good question I don't fully know the answer to,
Speaker 2: but I'm going to put a pin in it because
Speaker 2: I want to kind of get back to bio acids
Speaker 2: in a minute, okay, as it relates to our gut microbiome. Okay,
Speaker 2: So now the spores are activated, sea diff is replicating,
Speaker 2: and then somehow this leads to disease.
Speaker 4: How you may ask Aaron if you wanted to.
Speaker 2: I do okay, good, okay. Some species of sea diff.
Speaker 2: Not only do they form these spores in adverse conditions,
Speaker 2: but they also have the ability to produce toxins. And
Speaker 2: it turns out that it's these toxins, not the bacteria themselves,
Speaker 2: that are capable of causing infection aka sea diff colitis.
Speaker 2: So let's talk about what that actually looks like. Predominantly,
Speaker 2: se diff the toxogenic strains, the strains that produce toxins
Speaker 2: produce two major talks, very creatively named toxin A and
Speaker 2: toxin B. Keeps it easy, and essentially, what these two
Speaker 2: toxins do is they work together to ultimately disrupt the
Speaker 2: membranes of the cells that line your gut, and this
Speaker 2: results in little micro ulcerations of our gut wall, little
Speaker 2: little holes. It also disrupts the junction between cells which
Speaker 2: are supposed to be you know, a nice tight line
Speaker 2: of cells lining our gut. Basically, these toxins get in
Speaker 2: there and kind of shred the lining between them, leaving holes,
Speaker 2: which increases permeability, and that is what leads to watery,
Speaker 2: massive amounts of diarrhea. These toxins also then induce apoptosis
Speaker 2: and kill the cells that line our gut wall because
Speaker 2: of all of this disruption, and that leads to a
Speaker 2: lot of inflammation that can cause the formation of what
Speaker 2: are called pseudo membranes, which sounds gross and it looks gross.
Speaker 4: It's essentially just.
Speaker 2: Hordes of these dead cells mixed with bacteria and white
Speaker 2: blood cells and inflammatory gunk, and it forms this kind
Speaker 2: of membrane that then lines your gut, which even further
Speaker 2: prevents your colon from doing its job right of absorbing water,
Speaker 2: et cetera, which then leads to even more diarrhea.
Speaker 3: Okay, so I'm assuming that the benefit that seaediff gets
Speaker 3: from these toxins is that it can sort of wipe
Speaker 3: out the competition and even further and colonize as much
Speaker 3: as it wants to your intestines.
Speaker 4: Yeah, that's a good question.
Speaker 2: Maybe probably, I would guess, though, I mean, certainly it
Speaker 2: makes it hard for anything else to exist. Where these
Speaker 2: pseudo membranes exist.
Speaker 3: Okay, so it might not be necessarily helping with the colonization,
Speaker 3: but it helps clear the competition.
Speaker 2: Yeah, it's interesting because sea diiff is actually not a
Speaker 2: very good competitor to begin with, right, whether whether it's
Speaker 2: toxogenic or non toxogenic. So maybe these toxins are helping
Speaker 2: a little bit and making it a little bit more competitive.
Speaker 2: But I don't know for sure.
Speaker 3: Okay, toxins are costly to make m H, so you
Speaker 3: would think there'd be some sort of benefit from well toxins.
Speaker 2: I mean kind of like we've talked about in a
Speaker 2: lot of our bacterial pathogens that cause diarrhea. People who
Speaker 2: are having massive watery diarrhea because of sea diiff are
Speaker 2: spreading billions of spores, and spores, yeah, are very environmentally hardy,
Speaker 2: and so perhaps that's the major advantage, is that you're
Speaker 2: able to spread. Okay, I don't know if it's that satisfying,
Speaker 2: but but that's kind of the main and result. There's
Speaker 2: a lot more detail on these toxins. They're very interesting.
Speaker 2: There's also another toxin that is present in some strains
Speaker 2: that seems to when its present cause even more severe disease. Uh,
Speaker 2: But I'm not going to get into all of the
Speaker 2: specific biochemistry of it, because there's a lot more that
Speaker 2: I want to talk about with zetiff. But the end
Speaker 2: result of these toxins and the disruption that they cause
Speaker 2: in the lining of our colon, the death that they
Speaker 2: cause of the cells that line our colon, and all
Speaker 2: of this inflammation is what really causes the symptoms that
Speaker 2: we see.
Speaker 3: Is it only the toxogenic strains that cause disease?
Speaker 4: Okay?
Speaker 2: Yeah, And there are a lot of studies looking at
Speaker 2: do you have to have both of these toxins because
Speaker 2: it's toxin A and toxin B or could you have
Speaker 2: just one of these toxins. There's still some question as
Speaker 2: to that. It seems like in some models or in
Speaker 2: some clinical studies, they've seen that strains that only produce
Speaker 2: toxin B can still cause disease, so a might be
Speaker 2: kind of like a benefit but not necessary to cause disease.
Speaker 2: But then in other studies it looks like, no, you
Speaker 2: really have to have both, and if you only have
Speaker 2: one or the other, you don't really see disease from
Speaker 2: sea diiff, even though you might have colonization. So it's
Speaker 2: still a little bit I think up in the air.
Speaker 2: But it is really interesting the way that these two
Speaker 2: toxins kind of interact to then cause the actual symptoms
Speaker 2: that we see. Okay, so I've said the word symptoms
Speaker 2: like one hundred times, but I think the only thing
Speaker 2: I've said so far is diarrhea, and that is the
Speaker 2: hallmark symptom of a sea diiff infection, massive watery maybe
Speaker 2: mucis diarrhea. Generally, it's not overtly bloody diarrhea like we
Speaker 2: see with dysentery, and that's largely because seadift doesn't invade
Speaker 2: through our cells and it's very rare that it causes
Speaker 2: disease outside of the intestine. But because it is causing
Speaker 2: all of this inflammation and this damage to the lining
Speaker 2: of our gut, you can see like micro amounts of
Speaker 2: blood in the diarrhea, but usually not like what would
Speaker 2: look like bloody diarrhea. And otherwise symptoms can really really range.
Speaker 2: You can have very mild diarrhea with a set off
Speaker 2: infection to severe life threatening colitis that is the inflammation
Speaker 2: of your colon, of your gut wall. And even though
Speaker 2: it doesn't usually go outside of our colon and cause
Speaker 2: actual infection anywhere else. It can generate such a strong
Speaker 2: inflammatory response in our body that you see a lot
Speaker 2: of other signs of infectionate inflammation, a lot of abdominal
Speaker 2: pain with this infection, fevers, nausea, vomiting, generalized weakness because
Speaker 2: you're having diarrhea of all of your anything you're trying
Speaker 2: to eat, and so in severe cases, if this goes untreated,
Speaker 2: it can lead to significant dehydration, which can then lead
Speaker 2: to shock and death. It can also lead to something
Speaker 2: called toxic mega colon, which sounds horrific and talked about
Speaker 2: I think we have on shagus ah.
Speaker 4: Was it shaugus?
Speaker 1: Yep.
Speaker 2: Essentially, toxic mega colon is where your colon gets so inflamed.
Speaker 2: It's a very different mechanism here than in shagas disease,
Speaker 2: but it becomes very very distended and is unable to
Speaker 2: move any contents down your gut the way that it's
Speaker 2: supposed to, so gas and fecal contents just keep building up,
Speaker 2: and that can lead to perforation of your bells, which
Speaker 2: is of course a life threatening emergency.
Speaker 1: Yeah.
Speaker 3: I mean all of this sounds not only like painful
Speaker 3: and really unpleasant, but very life threatening.
Speaker 4: Very Yeah.
Speaker 2: So the mortality rate direct due to sea diiff infection
Speaker 2: is estimated to be about five percent, but that's just
Speaker 2: for death directly due to seedff infection, So sea diff
Speaker 2: colitis causing death. If you look at overall mortality that's
Speaker 2: associated with sea diff infection, which includes like downstream complications,
Speaker 2: but also just the fact that a large proportion of
Speaker 2: people who get sea diff infection are often already sick
Speaker 2: with underlying conditions, and so the kind of associated mortality
Speaker 2: rate is often up to fifteen to twenty five percent,
Speaker 2: Or if you look at people who are already in
Speaker 2: the ICU, so already like very sick, it's up to
Speaker 2: like thirty percent, which is horrific.
Speaker 3: Yeah, yeah, yeah and scary.
Speaker 2: It's really really scary. Yeah, sea diff is like the
Speaker 2: scourge of hospitals.
Speaker 4: But like I said.
Speaker 2: At the top, as severe as the infection that sea
Speaker 2: diiff causes can be, it doesn't always make us sick.
Speaker 2: It's an opportunistic pathogen and aarin. You'll probably talk more
Speaker 2: about this in the history section, So I hope I'm
Speaker 2: not stepping on your toes, but Claustridium difficile was actually
Speaker 2: first identified as just like a normal component of the
Speaker 2: microbiome in a healthy infants and neonates, what like, yeah, yeah,
Speaker 2: so this is a bacterium that might exist in me,
Speaker 2: or you, aaron, or in quite a lot of you listening,
Speaker 2: just as one of the I don't know how many
Speaker 2: hundreds of species happily coexist inside of our gut microbiome. Right,
Speaker 2: So then the question becomes who gets sick from sea
Speaker 2: diff and who lives with sea diff without ever getting
Speaker 2: sick and why? And the answer relates to two major things,
Speaker 2: one of which we've kind of already touched on. So
Speaker 2: first and most obviously, is is this a toxin producing
Speaker 2: strain or not? So not all strains of sea diiff
Speaker 2: produce those toxins. And because it's the toxins and not
Speaker 2: the bacterium that causes the damage, if you are colonized
Speaker 2: with a non toxogenic strain, you're very unlikely to get
Speaker 2: sea diiff colitis or seadiff infection. And there's actually some
Speaker 2: interesting studies, and I think this might be a little
Speaker 2: bit controversial because there just isn't a ton of data
Speaker 2: on it where they separate non toxogenic from toxogenic strains.
Speaker 2: But the data that does exist suggests that if you're
Speaker 2: colonized with a non toxogenic strain, it might actually be
Speaker 2: protective against infection with a toxogenic strain. But what's interesting
Speaker 2: is it doesn't seem to be an immune mediated response necessarily.
Speaker 3: Oh so it's like competition.
Speaker 4: Uh huh, let's talk about it a little more.
Speaker 3: I mean, does that just have to do with like
Speaker 3: the fact that it's a bad competitor and it's so
Speaker 3: needs like an open playing field.
Speaker 4: Yeah.
Speaker 2: So the other major thing other than strain that affects
Speaker 2: whether somebody gets Claustridium difficile infection or just is colonized
Speaker 2: with sea diff or has neither, like doesn't get seadiff
Speaker 2: infection and isn't colonized with sea diff is their microbiome
Speaker 2: and the composition of their microbiome to begin with. So
Speaker 2: I'm going to preface this by saying that all of
Speaker 2: the studies on the human microbiome, at least the ones
Speaker 2: that I read in specific how it relates to sea diiff,
Speaker 2: they're limited and have low sample sizes, So like, keep
Speaker 2: that in mind. But there's still some really interesting things
Speaker 2: from some review articles. So let me tell you what
Speaker 2: I found studies that have low at people colonized with
Speaker 2: sea diff versus not colonized with seed diff versus infected.
Speaker 2: Have found that people who test positive and have symptoms
Speaker 2: of infection with seed diff, so people sick from SEEDFF
Speaker 2: with seed diff colitis have a significant reduction in their
Speaker 2: overall microbial diversity and species richness. So for lots of
Speaker 2: people who don't know, because I even had to regogle,
Speaker 2: this species richness is just the actual number of different
Speaker 2: bacterial species that are present, and diversity is a measure
Speaker 2: of both that richness, so the number of species and
Speaker 2: the abundance of these different species. So people who get
Speaker 2: infected and get sick from seedediff have both low numbers
Speaker 2: of bacterial species in their gut and low diversity of
Speaker 2: those microbes. That's not surprising, right because we already said
Speaker 2: these are generally people who might be sick or that
Speaker 2: this is not a good competitor. But even people who
Speaker 2: are colonized with cluster named diffy Stiel without any overt
Speaker 2: signs of infection also have decreased species richness and diversity.
Speaker 2: But the distribution of species is different in these two groups.
Speaker 2: So it seems like there are certain species that are
Speaker 2: more protective against infection, and you know what, it seems
Speaker 2: like the effect of this microbiome composition on the amount
Speaker 2: of bio acids that make it all the way to
Speaker 2: your gut likely play a role.
Speaker 3: Interesting Okay, Okay, So but I have questions about this,
Speaker 3: uh huh. So this is what I think is difficult
Speaker 3: a lot about microbiome research, right, is that there's still
Speaker 3: so much we don't know, and so much is not
Speaker 3: necessarily about the species identity, like the species role, so
Speaker 3: like what's the functional role of those Like you might
Speaker 3: have two different species, but they might play a similar
Speaker 3: functional role.
Speaker 2: Right, And so that's why they think that at least
Speaker 2: they've been able to identify some of that in that
Speaker 2: the functional role of some of these species might be
Speaker 2: to decrease the amount of bio acids that activate seediff
Speaker 2: spores and therefore allow seedediff colonization activation and colonization.
Speaker 3: So then my second question is about the effect size.
Speaker 3: So like what when you say reduce the amount of
Speaker 3: bio like how much?
Speaker 2: Good question?
Speaker 4: I don't know.
Speaker 2: Okay, yeah, yeah, it basically just shifts the ratio of
Speaker 2: primary bile acids to secondary bio acids, but I don't
Speaker 2: know by what numbers.
Speaker 3: Okay, yeah, interesting, but it is really interesting.
Speaker 2: Yeah, I agree, even though I agree, we really don't know.
Speaker 4: And so it's also like, how do we then.
Speaker 2: Translate that into something that can then you know, prevent infection.
Speaker 2: It's still hard to do, right, Right, But what's important
Speaker 2: is that the biggest risk factor for ceediff colitis is
Speaker 2: antibiotic exposure, right. And it's not surprising when you look
Speaker 2: at that studies that have looked at even very short
Speaker 2: course exposure to antibiotics rapidly reduces the diversity of your
Speaker 2: microbiome in your colon. And this diversity, this reduction in
Speaker 2: diversity rather can persist for months and months, leaving you
Speaker 2: potentially susceptible to something like an opportunistic pathogen.
Speaker 3: Right, Because remember antibiotics are some are more targeted than others,
Speaker 3: but none of them are like this will only kill
Speaker 3: this species. It's there are going to be bystanders that
Speaker 3: are wiped out just as a result of taking antibiotics.
Speaker 2: Right, And any antibiotics that you take through your mouth
Speaker 2: are going to make it to your gut, so they're
Speaker 2: going to have some kind of an effect on your
Speaker 2: gut microbiome, even if the antibiotics are for a kidney
Speaker 2: infection or a skin infection, like it's going through your gut.
Speaker 1: Yeah.
Speaker 4: Yeah.
Speaker 2: The other risk factors for infection, of course, are things
Speaker 2: like exposure itself. And so the reason one of the
Speaker 2: reasons that seadiff infection is so pervasive in healthcare environments
Speaker 2: is because these spores exist in really really high concentrations
Speaker 2: in the feces of people with sea diiff infection, which
Speaker 2: means that they exist in really high concentrations at healthcare facilities,
Speaker 2: and they're so environmentally resistant that they're really hard to
Speaker 2: get rid of, and so they're really easily transmitted throughout
Speaker 2: healthcare systems.
Speaker 3: It's like a nightmare. It's yeah, that's how my grandmother
Speaker 3: got sick from SEEDFF after having a knee replacement, and
Speaker 3: it was it was horrible. I mean, it was absolutely
Speaker 3: It's just horrific.
Speaker 6: Yeah.
Speaker 4: Yeah. Yeah.
Speaker 2: Older age is also a really big risk factor.
Speaker 3: Yeah.
Speaker 2: So yeah, but it's not just healthcare. This just is
Speaker 2: getting more and more depressing because there are some studies
Speaker 2: that suggest that like thirty percent of people who end
Speaker 2: up with a sea diff infection don't actually have any
Speaker 2: risk factors, which also means that this isn't a problem
Speaker 2: only in hospitals or care facilities. This is also something
Speaker 2: that exists in the environment at large. So, and there
Speaker 2: are some studies in Europe, in places like the Netherlands
Speaker 2: that suggest that this what they're what they call community
Speaker 2: acquired sea diff aka not from a hospital, actually has
Speaker 2: a higher incidence than other causes of diarrhea that we
Speaker 2: think of that we might think are more common, like
Speaker 2: Camplobacter or sale manila. So it's a really important cause
Speaker 2: of diarrhea that not only can be fatal but also
Speaker 2: often causes recurrent infection. Yeah, so like ten to twenty
Speaker 2: five percent of people will get at least one recurrent
Speaker 2: infection after an initial infection, and of those people who
Speaker 2: get it twice, something like forty to sixty five percent
Speaker 2: of them may go on to have another and another.
Speaker 3: Just like MRSA.
Speaker 4: Again, yeah, exactly right. I think with c DIFF.
Speaker 2: It's one of those infections that it has become so
Speaker 2: clear how important the gut microbiome is to the establishment
Speaker 2: and persistence of an infection like this, or to the
Speaker 2: establishment and the susceptibility to an infection like this is.
Speaker 3: Yeah, it's it's kind of like the perfect example of like,
Speaker 3: oh hey, this thing that we didn't really think all
Speaker 3: that much about turns out that there's a very important
Speaker 3: balance and delicate balance, and the disruption of that is deadly.
Speaker 4: Yeah.
Speaker 2: Yeah, or it can be.
Speaker 5: Yeah, that's all for the biology are I mean, it
Speaker 5: is still a treatable infection a lot of the time,
Speaker 5: but again because.
Speaker 2: Of the recurrence and the resistance and the resistance. Well,
Speaker 2: the good news is that later in.
Speaker 4: This episode we are going to get to talk about.
Speaker 2: Fecal transplants mm hmmm, fecal microbiota transplants a ka f MT,
Speaker 2: putting healthy bacteria back into your colon. We'll talk more
Speaker 2: about it later, as well as other novel treatments and
Speaker 2: prevention strategies. But first, Aaron, tell me what's up with this?
Speaker 2: Where did it come from? Has it always been with us?
Speaker 2: Why is it making us so sick?
Speaker 3: Good questions? Good questions. I will try to answer them
Speaker 3: right after this break. The story that I want to
Speaker 3: tell for this history section is really more like two stories,
Speaker 3: each with a central main character to kind of origin stories,
Speaker 3: to rise of the villain or hero stories, and then
Speaker 3: only closer to the end, the two threads of the
Speaker 3: stories meet, and unlike most straightforward hero versus villain or
Speaker 3: good versus evil stories, the conflict doesn't drag on and on,
Speaker 3: although there's still a material for many sequels, but rather
Speaker 3: it resolves itself, I think, fairly quickly and in a
Speaker 3: satisfying way. So who are these two main characters? Tell me, Well,
Speaker 3: the first is probably fairly obvious because it's the topic
Speaker 3: of today's episode, and you've already gone in great detail
Speaker 3: about the biology of it, okay, Clostridium difficile. And the
Speaker 3: second might be pretty obvious to since we've also already
Speaker 3: talked about it. But I wanted to talk a bit
Speaker 3: about the history of fecal microbiotic transplantations or FMT, which
Speaker 3: are I think at least one of the obvious heroes
Speaker 3: in this story. And I also fully acknowledge that it's
Speaker 3: unfair and you know, anthropomorphizing to cast Seediff in the
Speaker 3: villain role, and that you know, these bacteria might be
Speaker 3: more accurately described as pawns without motive verguile, allowed only
Speaker 3: to cause the damage they do because of a human
Speaker 3: invention antibiotics. But I'm getting ahead of myself. And also
Speaker 3: I don't know how much time we need to spend
Speaker 3: in this particular episode about like anthropomorphizing of microbes and
Speaker 3: the symbolic language that we use, like battle and war
Speaker 3: on microbes whatever. It would be an interesting I would
Speaker 3: like to write a paper about that.
Speaker 4: That would be really interesting.
Speaker 3: Yeah, what words do we use? Because words matter? Anyway, Seediff,
Speaker 3: where did it come from? Well, the group Claustridium itself
Speaker 3: is incredibly ancient. It's estimated to have diverged from the
Speaker 3: bacterial domain about two point three four billion years ago,
Speaker 3: which is what I saw, and that's right around the
Speaker 3: same time that the atmosphere began to contain more and
Speaker 3: more oxygen. And while I don't know the exact specific
Speaker 3: origin of seaediff itself, I would imagine that based on
Speaker 3: its genome and its ability to coexist with humans and
Speaker 3: many other animals, it's been a part of our gut
Speaker 3: microbiota and the microbiota of many other animals for quite
Speaker 3: some time. And genomic analyzes of seediff also support this.
Speaker 3: The genome of a particular strain of seedff, I think
Speaker 3: one of the most predominant ones was fully sequenced and
Speaker 3: annotated around two thousand and six, and this analysis is
Speaker 3: a genomic look told us a lot about the ecology
Speaker 3: of this bacterium and the type of relationship that it
Speaker 3: has with its host like humans. So first, it told
Speaker 3: us that sea diiff is really well adapted to coexist
Speaker 3: with its host, not just to kill or pathogenically infect
Speaker 3: and cause disease, which is in contrast to a relative
Speaker 3: of seed Iff that we've talked about before, Claustridie and Bochelinum.
Speaker 3: So Clustridi and Bochulinum in contrast, contains many unique genes
Speaker 3: that are involved with like direct disease mortality, which is
Speaker 3: just I think that's interesting because that does speak to
Speaker 3: sort of the more multifaceted relationship that seediff has to humans.
Speaker 3: It's not necessarily just a pathogen.
Speaker 2: Right, So yeah, and it's and I mean it's not
Speaker 2: just a path right, So it's.
Speaker 3: A little bit it's a little bit deeper than that. Secondly,
Speaker 3: and one of the things that I find super interesting
Speaker 3: is that the species itself, like you know, all the
Speaker 3: isolates and strains and whatever that make up seed iff
Speaker 3: that we know about, they are incredibly diverse, even when
Speaker 3: compared to other bacterial species that have high genetic variability. So,
Speaker 3: according to one paper I read by night at All
Speaker 3: from twenty fifteen, the amount of shared core genome of
Speaker 3: seed iff, So in my understanding, that's the amount of
Speaker 3: genome shared across all isolates of seed iff, like the
Speaker 3: core genome or whatever is as low as sixteen percent,
Speaker 3: what which is lower than has been observed for any
Speaker 3: other bacterial species so far. And so what does that mean? Well, so,
Speaker 3: of course there's like natural genomic variation across members of
Speaker 3: an individual species like aaron, you and I, we don't
Speaker 3: share the same exact genome, right, But what this means
Speaker 3: is essentially that the amount of genomic variation across sea
Speaker 3: diiff is more along what you might expect for like
Speaker 3: members of a different genus, rather than among strains within
Speaker 3: a species. And so this research and other research has
Speaker 3: called into question Seaediff's designation as one species, with more
Speaker 3: researchers suggesting that we take a new approach to the
Speaker 3: taxonomy of seediff, so for instance, by recognizing certain strains
Speaker 3: as subspecies or separate species entirely, like the.
Speaker 4: Non toxogenic versus toxogenic that.
Speaker 3: Kind of something like that yeah, and so what does
Speaker 3: that mean in practice, I don't know, but I think
Speaker 3: it could have a lot to do, like, I don't
Speaker 3: know the evolution of this, trying to predict the evolution
Speaker 3: and the geographic spread, which wants to worry about, I
Speaker 3: don't know.
Speaker 4: It's also about.
Speaker 2: It would really change the way that we've gotten estimates
Speaker 2: for things like seediff colonization in the past, because right
Speaker 2: that it's been like all of these strains lumped together.
Speaker 3: Hmm, yeah, so it would it would definitely change like
Speaker 3: the disease burden or how we look at those numbers.
Speaker 4: Yeah. Yeah.
Speaker 3: So let's go back to when our villain, Seadiff was
Speaker 3: first discovered, or as it was first named Bacillis dificillis.
Speaker 3: And so, as you mentioned, Aaron, yes, this happened a
Speaker 3: long time ago, back in nineteen thirty five. Specifically, the
Speaker 3: name was changed to Claustridium difficile in nineteen thirty eight.
Speaker 3: And it happened when these two researchers in Denver, which
Speaker 3: I wanted to shout out because I don't think I've
Speaker 3: told everybody here on the podcast, but I moved to
Speaker 3: Denver this year and I love it. It's incredible, it's
Speaker 3: the best. But these two researchers were named Elizabeth O'Toole,
Speaker 3: and they collected the maconium and feces of ten newborn
Speaker 3: infants at a hospital to see what microbes might be
Speaker 3: in there. And I thought that was interesting because I
Speaker 3: guess I didn't realize that the characterization of the microbiome,
Speaker 3: or at least like the recognition of endosymbiotic bacteria, had
Speaker 3: started so early. And it's true that a lot of
Speaker 3: the early germ theory days were focused on like matching
Speaker 3: a disease to a pathogen, like, oh, we found a bacterium,
Speaker 3: it has to cause a disease, what does it cause?
Speaker 3: So you know, based on that, when people were just
Speaker 3: like hunting microbes, it does make sense that people would
Speaker 3: have encountered some over and over again that were not
Speaker 3: associated with any inherent or any apparent disease. But I
Speaker 3: think they're also Around this time, there had been a
Speaker 3: growing recognition that not all bacteria were bad, and that
Speaker 3: some might be helpful or at the very least neutral,
Speaker 3: And basically that's what it seems like Hall and Otool
Speaker 3: had set out to do with this study, just like
Speaker 3: find out what was there, and especially the way that
Speaker 3: these microbe communities changed during the first ten days after birth.
Speaker 3: And in their screening they found several species of bacteria
Speaker 3: that had already been described, but they also found something
Speaker 3: new in several of the samples. Quote an actively motile,
Speaker 3: heavily bodied rod with elongate, subterminal or nearly terminal spores
Speaker 3: of about the same diameter of the rods. Ooh man,
Speaker 3: what riveting reading riveting is right? And they named this
Speaker 3: new species Bacillis dificillis because of how difficult it was
Speaker 3: to isolate and study under lab conditions. It's just like
Speaker 3: a finicky guy.
Speaker 4: Finicky. It's anaerobic, you.
Speaker 3: Know, Yeah, they're finicky. Then, to see if they could
Speaker 3: figure out more about the role of this bacterium, they
Speaker 3: infected rabbits and guinea pigs with it to see what
Speaker 3: would happen, and they were surprised to find that it
Speaker 3: seemed white pathogenic to them, or at least that the
Speaker 3: bacterium produced a toxin that could lead to death or
Speaker 3: severe disease in these lab animals, although the toxins wouldn't
Speaker 3: be described until nineteen seventy four, when Green at All
Speaker 3: isolated it from the stools of guinea pigs treated with penicillin,
Speaker 3: although even then it was thought to be a virus,
Speaker 3: and that connection to seed iff wouldn't be made until later.
Speaker 3: And that's all kind of like part of the theme
Speaker 3: of seediff. It's like flying by under the radar, not
Speaker 3: really acting suspicious or you know, earning any suspicion. That
Speaker 3: kind of makes up a lot of the history of seediff.
Speaker 3: And so this paper that I talked about, the Hollino
Speaker 3: tool paper where seediff was first described, that came out
Speaker 3: in nineteen thirty five, and between the years nineteen forty
Speaker 3: and nineteen sixty two, there were only two mentions of
Speaker 3: seadiff infections in humans in the medical literature, and in
Speaker 3: both of these studies, seedediff was not suspected to be
Speaker 3: pathogenic to humans, like, it wasn't written about as a
Speaker 3: potential pathogen, and Hallan O'Toole did, like based on their
Speaker 3: rabbit and giddapig studies, they did say, oh, maybe we
Speaker 3: want to keep an eye out for this in infants
Speaker 3: as a possibility of causing disease, but it didn't. There
Speaker 3: didn't seem to be a whole lot of follow up
Speaker 3: and there didn't really seem to need to be a
Speaker 3: whole lot of follow up because it doesn't seem as though,
Speaker 3: at least from what I can tell, that there was
Speaker 3: a silent epidemic of sea diff during that time. So
Speaker 3: like since Hallan o'tool described it to I don't know,
Speaker 3: the nineteen fifties or something, and if anything, you know,
Speaker 3: I think I'm all side with you in being surprised
Speaker 3: at how early sea diiff was described, like nineteen thirty five.
Speaker 3: At first, I was like, wow, that's so recent, and
Speaker 3: then I was like, wait a second, Yeah, based on biology, No,
Speaker 3: that's like very surprisingly early.
Speaker 2: Right, especially because it was yeah, not causing disease, mhmm hmm.
Speaker 3: Yeah. And I definitely didn't find anything or read anything
Speaker 3: about historical infections of seediff or ancient writings describing the disease.
Speaker 3: I mean, you know, of course, there's plenty to choose
Speaker 3: from in terms of ancient writings of diarrhea. It's always
Speaker 3: been a part of human existence, and I'm sure that
Speaker 3: seadiff took on the role of pathogen occasionally in human history.
Speaker 3: And the first description we have of pseudomembranous colitis, for example,
Speaker 3: which is that horrible sounding condition caused by seediff is
Speaker 3: from eighteen ninety three, reported in a twenty two year
Speaker 3: old woman who had recently undergone surgery for a gastric tumor.
Speaker 3: She later developed severe diarrhea and died. And so maybe
Speaker 3: that was caused by sea diiff, but we have no
Speaker 3: way of knowing for sure. But beyond you know, cases
Speaker 3: like that, seedediff was probably just part of the background,
Speaker 3: like minding its own business, popping up here and there,
Speaker 3: and it likely would have stayed that way, just like
Speaker 3: a wallflower on your gut gut flower. But humans intervened,
Speaker 3: And of course I'm talking about the rise of antibiotics.
Speaker 3: So the widespread use of antibiotics began in the nineteen
Speaker 3: forties with penicillin, and it continued to grow and grow
Speaker 3: as more antibiotics, such as vankomycin were discovered and then administered.
Speaker 3: By the nineteen fifties, antibiotics were readily available everywhere and
Speaker 3: frequently prescribed, and the ones most commonly reached for were
Speaker 3: broad spectrum antibiotics, the ones that would wipe out not
Speaker 3: only whatever was making you sick, but a bunch of
Speaker 3: other species right along with it. Casualties of the War
Speaker 3: on Bacteria, and also like it's still reasonable to prescribe
Speaker 3: broad spectrum antibiotics, especially when you're someone sick and you
Speaker 3: don't know what it is and you need to try something.
Speaker 2: Yeah, it's still very important that they exist. And I'm
Speaker 2: not I am so yeah, yeah, we are still pro antibiotic, right.
Speaker 3: This isn't like antibiotics are not the are not part
Speaker 3: of the villain. They're they're just yeah.
Speaker 4: They're just a supporting character.
Speaker 3: Yeah, but this is an inevitable consequence.
Speaker 2: We are pro good antibiotics stewardship, Aaron.
Speaker 3: That is what we are pro. That's a very very
Speaker 3: important caveat there. Yeah. Okay, So shortly after the rise
Speaker 3: of antibiotics in the nineteen fifties and nineteen sixties, doctors
Speaker 3: began to notice a rise in pseudo membranous colitis, and
Speaker 3: a rise that seemed to be tied to antibiotic use.
Speaker 3: Surgeons had observed rates as high as fourteen to twenty
Speaker 3: seven percent among people who had recently undergone surgery.
Speaker 4: Which is high, that's very high.
Speaker 3: Yeah, And of course the prescription of antibiotics after surgery
Speaker 3: was and continues to be a very common practice and
Speaker 3: it's import and to prevent secondary infections. But even when
Speaker 3: people started to recognize the link between pseudomembranius colitis and antibiotics,
Speaker 3: ceedif wasn't really on the short or even long list
Speaker 3: of suspects. Most people actually thought that staph aureus was
Speaker 3: the likely culprit since it was often isolated from the
Speaker 3: patient's stool. And because of this, vancomycin, which was used
Speaker 3: to kill the staff, began to be given as the
Speaker 3: standard treatment for pseudomembranus colitis starting in the late nineteen fifties,
Speaker 3: but over the next couple of decades, staph orias seemed
Speaker 3: less and less likely to be the cause since it
Speaker 3: wasn't really reliably found in the stool of many people
Speaker 3: with pseudomembranus colitis, and the disease itself, like the rates
Speaker 3: of the disease didn't really seem to go down at all.
Speaker 3: A study in the nineteen seventies firmly displaced staph areas
Speaker 3: as the causative agent, and through suspicion on antibiotics themselves
Speaker 3: because they were like, well, if it's not staff, what
Speaker 3: the heck is it? And this study followed two hundred
Speaker 3: patients at a hospital who had been given clindamycin. Twenty
Speaker 3: one percent developed diarrhea and ten percent developed pseudomembranus colitis,
Speaker 3: but stool cultures were all negative for staphorus. And so
Speaker 3: it was this study and another study from New Zealand
Speaker 3: that linked diarrhea and colitis with antibiotics that kind of
Speaker 3: caught the wider attention of the medical community, including a
Speaker 3: doctor John G. Bartlett, who was then at Tufts University.
Speaker 3: So he had begun investigating antibiotic induced diarrhea and pseudomembranus
Speaker 3: colitis in the mid nineteen seventies, and in nineteen seventy
Speaker 3: eight he and his team published a series of papers
Speaker 3: in which they finally revealed the link between a toxin
Speaker 3: producing class stridium and pseudomembranus colitis. And then he followed
Speaker 3: up this research by showing that he had found seediff
Speaker 3: in the stool samples of several of the individuals in
Speaker 3: that first study of two hundred patients that they could
Speaker 3: find no staff, they were like, well, we don't know
Speaker 3: what it is. And so he actually got some of
Speaker 3: those samples and was like, seadiffs here as well, so
Speaker 3: that kind of was just like boom. This clearly made
Speaker 3: the link, and he went on to uncover a great
Speaker 3: deal more about seediff, which also hugely opened up the
Speaker 3: field for other researchers to characterize its toxins, to examine
Speaker 3: strain diversity, and to understand transmission dynamics. Like from the
Speaker 3: late nineteen seventies to now, we know an incredible amount
Speaker 3: about this bacterium. It's pretty amazing, I mean, and that
Speaker 3: also speaks to the huge public health impact that it has.
Speaker 3: With these late nineteen seventies studies from Bartlett and his group,
Speaker 3: the field of sea diiff was blown wide open. It
Speaker 3: seemed that once researchers started looking for the pathogen, they
Speaker 3: found it everywhere, and in increasingly high numbers. The continued
Speaker 3: use of antibiotics, especially cephalosporins, which seadiff is intrinsically resistant to,
Speaker 3: during the nineteen eighties and nineteen nineties it led to
Speaker 3: a huge rise in seaediff overall, which of course led
Speaker 3: to a huge increase in the diversity of strains, including
Speaker 3: the emergence of highly virulent strains, and over time, the
Speaker 3: characterization of seediff as a hospital acquired pathogen and one
Speaker 3: that you have nothing to worry about if you aren't
Speaker 3: in a hospital, or if you don't work in a
Speaker 3: hospital setting, or if you aren't taking antibiotics, like you said, Aaron,
Speaker 3: that's become increasingly less accurate. Community acquired infections have become
Speaker 3: more common, as I read have animal associated infections, either
Speaker 3: through direct contact as well as potentially food borne, which
Speaker 3: has led to many people calling for a one health
Speaker 3: approach for this pathogen. Oh, I know, one health always well.
Speaker 2: Yeah, but this, like the numbers that I saw on
Speaker 2: like ground meats being contaminated, was terrifying.
Speaker 3: Are you going to share them?
Speaker 1: Oh?
Speaker 2: I didn't write them down, but I should pull them
Speaker 2: back up because it is awful.
Speaker 1: Okay.
Speaker 3: Yeah. Because also the other thing, and we touched on
Speaker 3: this in I think our antibiotics episode, we had to
Speaker 3: have maybe the second one. The overuse of antibiotics in
Speaker 3: both livestock and like other animals has led to increasingly
Speaker 3: resistant and difficult to treat strains of sea diff Sea
Speaker 3: diiff is now like quite expectedly an enormous global problem,
Speaker 3: which I know you'll get into more later.
Speaker 4: Yeah.
Speaker 3: It had this dramatic rise from zero to villain that
Speaker 3: was made possible only buy antibiotics. So maybe it's time
Speaker 3: we looked for and out of the box solution or
Speaker 3: out of the bowl solution.
Speaker 2: I don't know, no, no, okay, Oh goodness.
Speaker 3: So you know the saying like fight fire with fire?
Speaker 4: Oh sure, what about.
Speaker 3: Fighting poop with poop?
Speaker 4: Oh? Aaron?
Speaker 3: You know I can't resist to come on, I love it.
Speaker 3: I do introducing fecal microbiota transplants. So at the end
Speaker 3: of this episode you'll get to hear a whole lot
Speaker 3: more about the how and the why of fecal microbiotic transplants,
Speaker 3: and I can't wait to get into it, but I
Speaker 3: wanted to first provide a bit of context, a bit
Speaker 3: of the where did this come from? And how did
Speaker 3: we get to where we are today type of thing. Essentially,
Speaker 3: like you said, Aaron, the idea behind fecal microbiota transplants
Speaker 3: is that you take the fecal material from a healthy
Speaker 3: donor and put it in the intestinal tract of someone
Speaker 3: who has some sort of GI disorder, often because their
Speaker 3: microbiota is disrupted, and you do this in order to
Speaker 3: change the gut microbiota, the composition of the microbes in
Speaker 3: the gut with the hope that this infusion acts like
Speaker 3: a hard reset and can take out the disease, kind
Speaker 3: of get things.
Speaker 2: Back to normal, like unplug it and pluck it back
Speaker 2: in again.
Speaker 3: Exactly, And it works in many cases, like remarkably. Well,
Speaker 3: it's beautiful, Like it's a beautiful thing. I love it.
Speaker 3: I get chills when I think about FMT's They're just
Speaker 3: so satisfyingly wonderful.
Speaker 4: It's so elegant.
Speaker 3: Yeah, it is.
Speaker 2: It's weird to say because it's poop, but it is.
Speaker 3: I think it's it's the simplicity of it and the
Speaker 3: logic of it is so of course.
Speaker 4: Yeah.
Speaker 3: Yeah, So who first came up with this idea that
Speaker 3: healthy poop could cure someone's bad poop?
Speaker 4: Yeah, I don't know. Tell me.
Speaker 3: It actually goes way way back, all the way back
Speaker 3: to the fourth century in China.
Speaker 1: CE.
Speaker 3: Yeah, fourth century CE.
Speaker 2: I love that erin And it is somehow shocking and
Speaker 2: also not surprising at all if you've ever listened to
Speaker 2: this podcast, I feel.
Speaker 3: Like exactly, yeah.
Speaker 4: Yeah.
Speaker 3: So it was described in the first Chinese Handbook of
Speaker 3: Emergency Medicine, and in this book it was recommended that
Speaker 3: if you had food poisoning or severe diarrhea. You should
Speaker 3: ingest fecal suspension by mouth. Wow mm hmmm. And it
Speaker 3: was described as not just being like somewhat successful, like oh,
Speaker 3: try this and it might work, but like miraculous bringing
Speaker 3: back patients from the brink of death. And this isn't
Speaker 3: the only reference to early fecal transplants either. In the
Speaker 3: traditional Chinese medicine book Compendium of Materia Medica, a series
Speaker 3: of prescriptions are described that are essentially various preparations of
Speaker 3: human fecal material. I've got your fermented fecal solution, fresh
Speaker 3: fecal suspension, dry feces, infant feces, take your pick all
Speaker 3: for the effective treatment of abdominal diseases with severe diarrhea, fever, pain, vomiting,
Speaker 3: and constipation, just various things. And so reading about this
Speaker 3: got me thinking about all of the times that we
Speaker 3: have laughed and laughed and laughed about ancient or medieval
Speaker 3: cures and how ridiculous they are.
Speaker 4: I know, I know.
Speaker 3: And it struck me that if we had done this podcast,
Speaker 3: this episode twenty or thirty years ago, we may have
Speaker 3: similarly laughed at yellow soup, at actually eating poop. But
Speaker 3: we're not laughing now, except that ourselves. Maybe that's Yeah,
Speaker 3: that's hard, Aaron, I know, and that's not to say,
Speaker 3: but I'm not saying that. Hey, maybe we should look
Speaker 3: into how effective saying my work be with you is
Speaker 3: for treating HPV or like mice tails for rabies or something.
Speaker 3: But it is a good reminder that every generation thinks
Speaker 3: of themselves as being so advanced and looks down on
Speaker 3: past generations with scorn like how on earth could they
Speaker 3: have believed something like that? And so maybe we shouldn't
Speaker 3: be so quick to dismiss the ideas of the past.
Speaker 3: And this is I'm super guilty of this, of like,
Speaker 3: how look at these cures? These are ridiculous.
Speaker 2: I know we all need to be more open minded,
Speaker 2: don't we.
Speaker 4: We do? I think so.
Speaker 3: Yeah, And even if they are clearly not based in
Speaker 3: any sort of medicine or like clearly they would not
Speaker 3: be effective, I think it also is still useful to
Speaker 3: at the very least try to understand the logic or
Speaker 3: reasoning behind them. Why mice tails ground with wine or
Speaker 3: pigeon heart and beer or something like that, Like, right,
Speaker 3: what about that? Because if there's one thing that's an
Speaker 3: absolute certainty it's that future generations will look back on
Speaker 3: us now in our medical practices or scientific knowledge that's
Speaker 3: widely accepted today, and they'll think, how on earth could
Speaker 3: they have thought that? Or oh, my god, did they
Speaker 3: not realize that they were only making things worse?
Speaker 2: I think that almost every day, Yarin Ah.
Speaker 3: Yeah. And the examples of this, I think are endless,
Speaker 3: like our limited understanding of autoimmune disorders, or the mechanisms
Speaker 3: behind different mental health issues, or some of the ways
Speaker 3: that we treat cancer, or how we over use antibiotics. Like,
Speaker 3: there's a lot there that people will have. There's ample
Speaker 3: material for people to laugh at us in the future.
Speaker 3: But we think we know it all now.
Speaker 2: We're all just doing our best.
Speaker 3: We're all just doing our best. But my point is,
Speaker 3: I think that we can look back and see how
Speaker 3: far we've come with these things with our knowledge and technology,
Speaker 3: and maybe feel okay, laughing a bit about my warp
Speaker 3: be with you, just because it's such a great saying.
Speaker 3: But I think we also need to recognize that there
Speaker 3: is still so far to go, and that scientific or
Speaker 3: medical advancements are rarely, if ever, done in leaps and bounds,
Speaker 3: but rather the accumulation of years and years and centuries,
Speaker 3: sometimes of shared knowledge being built. All right, so soapbox moment.
Speaker 3: Beyond those early descriptions of yellow soup and poop as
Speaker 3: treatment from China, there are a couple of other examples
Speaker 3: of what is essentially fecal microbiota transplants from other parts
Speaker 3: of the world. In the seventeenth century, there was an
Speaker 3: Italian anatomist who wrote, quote, I have heard of animals
Speaker 3: which lose the capait to ruminate, which when one puts
Speaker 3: into their mouth a portion of the materials from the
Speaker 3: mouth of another ruminant which that animal has already chewed,
Speaker 3: they immediately start chewing and recover their former health. And
Speaker 3: he called that process transformation. And also, like, I just
Speaker 3: want to point out that many animals regularly consume feces
Speaker 3: for oh, probably a variety of reasons.
Speaker 4: My dog loves it.
Speaker 3: Yeah, dogs love poop. And then later on in the
Speaker 3: seventeenth century, also a German physician recommended fecal transplant for
Speaker 3: humans in a book whose title translates to either healing
Speaker 3: mud pharmacy or salutary filth pharmacy, depending on the source. Like,
Speaker 3: I found it translated both ways, so I don't know.
Speaker 3: I also saw it mentioned that Bedouin groups historically consumed
Speaker 3: camel stools as treatment for bacterial dysentery, something that seems
Speaker 3: to have been picked up on during World War Two,
Speaker 3: when German soldiers were dying of dysentery in Africa, Nazi
Speaker 3: scientists observed that locals would consume fresh camel stools at
Speaker 3: the first sign of disease, and it seemed to prevent
Speaker 3: them from getting sick. And so the scientists cultured what
Speaker 3: they could find in the stools, and they isolated Bascilla subtilis,
Speaker 3: which they cultured and administered to decent success. Like it
Speaker 3: seemed to work to a certain extent, So that's kind
Speaker 3: of cool. It's like this all goes way back further
Speaker 3: than I thought. Yeah, But from then, as far as
Speaker 3: I can tell, the concept of fecal microbiota transplantation it
Speaker 3: really only remained mostly in practice or even in experimentation
Speaker 3: in veterinary medicine until nineteen fifty eight, when Iceman and
Speaker 3: colleagues successfully used fecal microbiota transplants to treat four people
Speaker 3: with pseudomembranous colitis with antibiotic use, this time fortunately using
Speaker 3: an enema rather than oral application.
Speaker 4: Nineteen fifty eight.
Speaker 3: Yeah. Wow, Yeah, And this kind of just goes like
Speaker 3: to further show that developments are not made in isolation,
Speaker 3: like a lot of there's a lot of background to things,
Speaker 3: because in this study he wrote that quote, most of
Speaker 3: the recently reported cases of pseudomembranous colitis have followed the
Speaker 3: use of oral broad spectrum antibiotics, suggesting that the intestinal
Speaker 3: flora was thus altered to permit the overgrowth of antibiotic
Speaker 3: resistant micrococcus pyogenies within the gut.
Speaker 2: Huh.
Speaker 3: And so, yeah, he didn't get the bacterial species right necessarily,
Speaker 3: but all you have to do is swap out micrococcus
Speaker 3: pyogenies for seed if And he's absolutely right in this
Speaker 3: mechanism of how broad spectrum antibiotics like perfectly set up
Speaker 3: the gut for something to take over. Yeah, but decades
Speaker 3: would pass before the idea of the fecal microbiotic transplant
Speaker 3: would gain any real traction in human medicine, especially as
Speaker 3: more antibiotic classes were discovered. Being like, oh, well we
Speaker 3: can fix that, Oh we can fix that this way.
Speaker 4: You know.
Speaker 3: It kind of reminds me a bit of like how
Speaker 3: phage therapy dropped out. Yes, yeah, and it was used again.
Speaker 3: Fecal microbida transplants were used again in nineteen eighty nine
Speaker 3: to treat someone with refractory alterative colitis, and it was
Speaker 3: remarkably successful with lasting recovery. But for the most part,
Speaker 3: reports of people successfully using fecal microbiotic transplants were kind
Speaker 3: of like one offs, like these, you know, case studies
Speaker 3: of people trying out fecal microbida transplants for a variety
Speaker 3: of infectious and non infectious conditions on one patient, on
Speaker 3: a handful of patients, but not like large scale. It
Speaker 3: wasn't until twenty thirteen that the first randomized clinical trial
Speaker 3: was conducted in the Netherlands to look at fecal microbiota
Speaker 3: transplant as a treatment for sea diiff infections. Here's where
Speaker 3: our two our villain and our hero meet took a while,
Speaker 3: but hey, and you'll see that it soon is resolved
Speaker 3: because in this study the participants all had recurren se
Speaker 3: diff and they were all randomly assigned to one of
Speaker 3: three groups, either receiving vancom iosin alone, vancom iasin with
Speaker 3: bowel levage, or bowl levage, and then fecal microbiota transplant
Speaker 3: as treatment. And although the study was initially supposed to
Speaker 3: include one hundred and twenty people with forty people in
Speaker 3: each group, it was stopped early with only forty three participants.
Speaker 3: Why was it stopped because it was so incredibly successful
Speaker 3: that it wasn't ethical to keep going with the other
Speaker 3: control groups when fecal microbiotic transplant showed such incredible cure rates.
Speaker 4: Wow.
Speaker 3: Yeah, So of the nineteen people in the fecal microbiota
Speaker 3: transplant group, ninety four percent were cured of sea diff infection. Wow,
Speaker 3: after a couple rounds of treatment of like eighty something
Speaker 3: were cured after one ninety four percent cured cured.
Speaker 2: And that means like no more recurrences.
Speaker 3: No more recurrences, compared to thirty one percent of those
Speaker 3: in vancomized and only groups and twenty three percent of
Speaker 3: those in the vancomizon plus bowel levage groups. So like, yeah,
Speaker 3: I mean leaps and bounds beyond Yeah, the ability of antibiotics.
Speaker 3: So that's I just I love that. What a clear
Speaker 3: indication of like, hey, there's real promise here. Yeah. And
Speaker 3: after the study was stopped, the people who we're in
Speaker 3: the vancomycin groups were treated with fecal transplants, and they
Speaker 3: also showed high rates of cure. But how exactly do
Speaker 3: they work? How do fecal microbiota transplants work, What diseases
Speaker 3: or conditions do they seem to be effective against? How
Speaker 3: does one become a stool donor what makes someone a
Speaker 3: good candidate for fecal microbida transplants? Are their long term consequences.
Speaker 4: We have so.
Speaker 3: Many questions about fecal microbiota transplantation, and thank goodness we
Speaker 3: have an actual expert to help us answer them. But
Speaker 3: before we get to that, I think that Aaron, I
Speaker 3: want you to tell me just how much the world
Speaker 3: needs creative solutions like fecal microbida transplants for this incredibly
Speaker 3: enormous global seediff problem.
Speaker 2: I would love to right after this break. So we're
Speaker 2: starting off this season two episodes in a row with
Speaker 2: not great numbers. When it comes to we should have
Speaker 2: thought this, we didn't know.
Speaker 3: Listen, of all of the diseases, I would have expected
Speaker 3: seedift to have good numbers.
Speaker 4: Yeah, I would have. Let me tell you what I've got.
Speaker 2: Estimates in the US and from what I can tell
Speaker 2: these numbers that get thrown around seem to be from
Speaker 2: like twenty eleven is where they're getting these estimates.
Speaker 3: That's a long time ago, like in ten years ago.
Speaker 2: Yeah, yeah, but that's what we're working with here aarin.
Speaker 2: The US estimates about five hundred thousand, half a million
Speaker 2: cases a year and twenty nine thousand deaths due to
Speaker 2: see diff infection. Now, that number in the studies that
Speaker 2: I read was thought to be a huge underestimation, but
Speaker 2: that's still the number that the CDC sites on their website,
Speaker 2: for example today here in twenty twenty one.
Speaker 3: I was going to say, that sounds lower than I
Speaker 3: would have thought.
Speaker 4: Yep.
Speaker 2: The European Center for Disease Prevention and Control in the
Speaker 2: same year twenty eleven was estimating one hundred and twenty
Speaker 2: four thousand cases a year and didn't have a real
Speaker 2: estimate on deaths that I found, wait, all across Europe.
Speaker 2: That was Yeah, the European Center for Disease Prevention and Control. Now,
Speaker 2: I obviously wanted to get better numbers than that, so
Speaker 2: I was trying to find global estimates. I found a
Speaker 2: paper that was a meta analysis from a couple of
Speaker 2: years ago that looked at a whole bunch of different
Speaker 2: papers and calculated an average number of SEADIFF infections for
Speaker 2: every one thousand hospital admissions worldwide. And they calculated an average,
Speaker 2: a global average of two point two five cases of
Speaker 2: SEADIFF infection for every one thousand hospital admissions worldwide. And
Speaker 2: I was like, wait a second, that number doesn't make
Speaker 2: a lot of sense.
Speaker 4: And if you look in.
Speaker 2: That paper at the ranges with which they calculated this average,
Speaker 2: the ranges are bananas. They're from anywhere from one case
Speaker 2: per one thousand to thirty seven cases per one thousand
Speaker 2: hospital admissions, depending on which geographic region you look at.
Speaker 2: North America by far has the greatest number of cases
Speaker 2: reported compared to other places. And even though this study
Speaker 2: looked at forty one different countries, there was no data
Speaker 2: whatsoever from South America, or from Africa, or from a
Speaker 2: lot of countries in Asia.
Speaker 3: So still we don't have great numbers.
Speaker 2: We still don't have great numbers.
Speaker 3: Okay, but the twenty nine thousand deaths and half a
Speaker 3: million cases in the US in twenty eleven was an
Speaker 3: underestimation then and likely continues to be an underestimation.
Speaker 2: Yes, I did a little bit of aerin math.
Speaker 4: You know my trademark.
Speaker 3: I love aerin math.
Speaker 2: Me too, trademark airin math. Don't trust these numbers. So,
Speaker 2: according to the American Hospital Association, and that's just in
Speaker 2: the US, there are over thirty six million hospital admissions
Speaker 2: every year in the US alone. So if you look
Speaker 2: at those estimates of like maybe it's as low as
Speaker 2: two and a half, it isn't cases of seadiff per
Speaker 2: one thousand hospitalizations or as high as thirty seven per
Speaker 2: one thousand. That's anywhere from eighty thousand to over one
Speaker 2: point two million cases in US hospitals alone each year.
Speaker 3: It's quite arranged. Plus it's not just hospitals, Like what
Speaker 3: about long term care facilities?
Speaker 4: Exactly?
Speaker 2: Exactly that's the problem. And we just with a lack
Speaker 2: of surveillance in a lot of places, and sometimes even
Speaker 2: a lack of definitions on how are you testing or
Speaker 2: screening for seadiff infection versus colonization? How are you even
Speaker 2: defining a seadiff infection? It makes global estimates really really difficult.
Speaker 3: Well, I think we can come up with a qualitative
Speaker 3: metric based on the biology of the disease as well
Speaker 3: as our medical practices of you know, using a lot
Speaker 3: of antibiotics for a good reason, right, and that it's
Speaker 3: probably been only increasing since it was very first scene
Speaker 3: and I mean skyrocketed in terms of numbers, and now
Speaker 3: it's everywhere and it's a huge problem.
Speaker 4: It really is.
Speaker 2: So because of that, there are a lot of areas
Speaker 2: of research ongoing when it comes to SEEDFF. Even though
Speaker 2: it seems like future areas, a lot of this research
Speaker 2: is promising enough that there are things that are not
Speaker 2: future future directions of research there present. The very first
Speaker 2: thing is probiotics. Probiotics are an area of research that
Speaker 2: I think is really fascinating. It all goes back to
Speaker 2: the whole microbiome, which we don't know a lot about.
Speaker 2: But there was a Cochrane review from twenty seventeen that
Speaker 2: showed with moderate certainty evidence, which is like pretty good
Speaker 2: for a Cochrane review, that probiotics can reduce the risk
Speaker 2: of seediff infection by as much as sixty percent in
Speaker 2: people who are inpatient in the hospital on antibiotics. So
Speaker 2: giving probiotics concurrently with antibiotics might be significantly protective.
Speaker 3: This is like opening a huge can of worms, but like, yeah.
Speaker 2: I I know, and it was a part review.
Speaker 4: What does that mean exactly?
Speaker 2: I don't have data on like what that actually means
Speaker 2: in practice, because, yeah, probiotics, they're not exactly regulated. We
Speaker 2: don't know enough about the human microbiome to know what
Speaker 2: are these specific bacteria and which probiotics do you take?
Speaker 2: And how much money are you supposed to spend on
Speaker 2: these things.
Speaker 4: Et cetera.
Speaker 3: And things that are claiming to be probiotic, but like are.
Speaker 4: They actually probatic? Right, Like exactly what do.
Speaker 3: You need to do to have probatic on your label?
Speaker 4: That I don't have an answer too.
Speaker 3: But things to think about, things to think about.
Speaker 2: And they did mention yogurt specifically multiple times in this
Speaker 2: that makes sense, So I don't know.
Speaker 3: And I'm also I'm all for probiotics, but me too,
Speaker 3: like we got to ask questions.
Speaker 2: But yeah, so that's kind of a one thing now
Speaker 2: that seems to be really promising, and I don't think
Speaker 2: that it's really talked about enough. And it's likely because
Speaker 2: of all the problems that are inherent, like we already
Speaker 2: said with the idea of probiotics, that we just don't
Speaker 2: have good regulation on them. We don't know a lot
Speaker 2: about them. But that doesn't mean you can't find places
Speaker 2: that have live cultures of bacteria and help yourself. I
Speaker 2: don't know other things there are. Even though antibiotics are
Speaker 2: still used very commonly for treatment of seediff, we know
Speaker 2: that antibiotic resistance is a huge problem. There are a
Speaker 2: number of different monoclonal antibodies that have been shown to
Speaker 2: be beneficial for the treatment of especially recurrent seediff infection.
Speaker 2: That would be something that's only available, you know, in
Speaker 2: the case where you're already really, really sick. It's not
Speaker 2: necessarily preventing you. There are also a lot of different
Speaker 2: vaccine candidates that have been studied. Generally these are toxoid vaccines,
Speaker 2: so vaccines against just the toxins A and B to
Speaker 2: help prevent infection from seediff rather than just colonization. But yeah,
Speaker 2: there's a lot of promise both in terms of how
Speaker 2: we can potentially deal with especially severe seaediff infections today
Speaker 2: but going forward, how we might be able to prevent
Speaker 2: them even more down the line. But here on TPDKY,
Speaker 2: we all have our biases, and one of ours is
Speaker 2: how amazing fecal microbiotic transplantation is.
Speaker 3: Yeh, I don't think we've been in enthusiastic enough about
Speaker 3: it this episode.
Speaker 4: It is truly like the first time that.
Speaker 2: I heard about it, I was just so enthused, like
Speaker 2: I want to be a donor and or I want
Speaker 2: a transplant for just because I think it's amazing.
Speaker 3: I think it's it is like you said, it's just
Speaker 3: like you know, Chef's kiss. Yes, beautiful.
Speaker 4: I love it.
Speaker 2: So we were absolutely thrilled to speak with a true
Speaker 2: expert from Open Biome, which is a nonprofit organization that
Speaker 2: is all about expanding access safe access to fecal microbiota
Speaker 2: transplant and increasing research into.
Speaker 4: The human microbiome.
Speaker 2: We'll let them introduce themselves right now.
Speaker 6: I'm Majdi. I am the chief medical officer at open Biome,
Speaker 6: and I'm a physician trained in infectious diseases, as you
Speaker 6: could probably tell by the accent, trained in the UK,
Speaker 6: and my first encounter with FMT was about ten years
Speaker 6: ago now and a patient who an elderly woman who
Speaker 6: had seed of facial infection after a hip operation and
Speaker 6: we'd run out of options for her. The sort of
Speaker 6: next thing on the treatment ladder was surgery, which for
Speaker 6: a frail patient like this was going to come with
Speaker 6: a lot of risks, and so this was before stool banks.
Speaker 6: We had to do the FMT ourselves from a related
Speaker 6: donor of the patient, and you know, within three days
Speaker 6: the patient had fully recovered from their seed iff and
Speaker 6: was eating and ready to go home. So that was
Speaker 6: sort of my first encounter with this treatment. It wasn't
Speaker 6: until I came to the US that and met the
Speaker 6: team at Opened Biome just as things were getting started
Speaker 6: that I ended up embarking on this adventure.
Speaker 3: Yeah, that's amazing. So talking now about open Biome, can
Speaker 3: you tell us a about the project and sort of
Speaker 3: what a nonprofit stool bank is, you know, how did
Speaker 3: it get started and what are some of its missions?
Speaker 6: Yeah, yeah, so open bind we're a nonprofit stool bank.
Speaker 6: As he said, you know, our first mission is to
Speaker 6: enable safe access to this treatment fecal microbarri to transplants
Speaker 6: or FMT, and the second half of our mission is
Speaker 6: to castalyize research in the human gut microbiome using FMT,
Speaker 6: but also other tools in our toolkit to support new
Speaker 6: ways of understanding and treating diseases, especially those in areas
Speaker 6: of unmet need. And we started really because of our
Speaker 6: executive director Carolyn. She had a relative that, you know,
Speaker 6: a young guy in his early twenties, just out of college,
Speaker 6: you know, had a gold badder infection, had surgery and
Speaker 6: then some antibiotics after that, and developed cedificile infection and eventually,
Speaker 6: you know, having found out that he would have had
Speaker 6: to wait several months for an FMT, he would have
Speaker 6: had to drive hours to one of hospitals in New
Speaker 6: York to get this treatment, decided to take matters into
Speaker 6: his own hands and ended up doing an FMT himself.
Speaker 6: And so, you know, that was sort of the motivating
Speaker 6: patient in a way for us to establish Open Biome
Speaker 6: really to make sure that patients who had seedificil infection,
Speaker 6: who had failed antibiotic therapy didn't have to go through
Speaker 6: that process again of having to source their own donor
Speaker 6: and getting their own treatment arranged, and to make this,
Speaker 6: as you know, as straightforward as getting a blood transfusion.
Speaker 6: And so you know, we set ourselves up really to
Speaker 6: serve that need. And yeah, we've grown to the point
Speaker 6: now where we work with over a thousand hospitals across
Speaker 6: the US and ninety nine percent of the US population
Speaker 6: is within a four hour drive of a hospital. Using
Speaker 6: open FMT.
Speaker 3: That is amazing. What an origin story. I can't believe that,
Speaker 3: but I mean it's clear that over the years the
Speaker 3: need for FMT's is more and more pressing. And so
Speaker 3: it's an incredible thing that you guys are doing. And
Speaker 3: So before we get further into the transplant aspect of this,
Speaker 3: I want to talk about donation, like what is a
Speaker 3: stool bank and also how does one become a donor?
Speaker 3: What are their criteria for acceptance? Like I have a
Speaker 3: lot of questions, but we'll start there.
Speaker 6: Yeah, sure, think so the stool bank is a bit
Speaker 6: like a blood bank really, but for poop. So what
Speaker 6: we do is we screen our donors. We're based in
Speaker 6: Boston and so all of our donors come from around
Speaker 6: this area. A bit like with a blood transfusion, we
Speaker 6: would screen our donors to make sure that they aren't
Speaker 6: potentially passing on any risk of either infection to a
Speaker 6: recipient or potentially some of these other diseases that we
Speaker 6: seem to see in association with the gut microbiome. You know,
Speaker 6: these are things like asthma, diabetes, obesity, even mood disorders
Speaker 6: like depression or anxiety. And so you know, we put
Speaker 6: these donors through a pretty comprehensive screening process, which starts
Speaker 6: off initially with an online form that if anyone is
Speaker 6: interested in becoming a donor, they go to our website
Speaker 6: fill out a short form that excludes for the common
Speaker 6: reasons that folks are ineligible to become a donor. And
Speaker 6: so then if a prospective donor completes that form and
Speaker 6: it's all clear, then they would be invited for an
Speaker 6: in person clinical assessment led by one of our clinical
Speaker 6: team that includes a clinical assessment where they run through
Speaker 6: nearly two hundred questions related to their health, physical assessment,
Speaker 6: and then if they pass that, they go through a
Speaker 6: blood and a stall test, and yeah, it doesn't stop
Speaker 6: there though, you know. If a donor passes all of that,
Speaker 6: then they have an assessment each time they drop off
Speaker 6: a stall sample, and then every sixty days they undergo
Speaker 6: the same three step screen. So the clinical all the
Speaker 6: blood in the stool. The past rate for becoming a
Speaker 6: donor is less than three percent, and so we often
Speaker 6: say that it's harder to become a donor open biome
Speaker 6: than it is to say, get into MIT or HAVID
Speaker 6: because we are sort of screening these folks really rigorously.
Speaker 3: Wow, that is very interesting. What a thorough process. I mean,
Speaker 3: it completely makes sense. But so now I want to
Speaker 3: switch to transplants. What are FMT's fecal microbiotic transplants and
Speaker 3: how do they work? Could you walk us through like
Speaker 3: the entire process from the patient's perspective.
Speaker 6: Sure, So, a fecal microbiot to transplant or an FMT
Speaker 6: is a very simple treatment in a lot of ways.
Speaker 6: It's essentially taking stool from a healthy donor and transferring
Speaker 6: it to a patient who's got a disease, in this
Speaker 6: case ceoficile infection. And you know, when a donor who's
Speaker 6: been screened and gone through that very rigorous process provides
Speaker 6: a sample, that sample is inspected, tested, and then simply
Speaker 6: we add a saline glyceryl buffer so that it stays stable.
Speaker 6: Once it's frozen, we homogenize it or blend it and
Speaker 6: then filter it to remove any anything like food debris
Speaker 6: or other things that aren't relevant for the treatment. And
Speaker 6: so then that treatment gets frozen, either as a liquid
Speaker 6: preparation that is instilled via colonoscopy or via a par
Speaker 6: endoscopy or nasogastric tube, or alternatively we prepare it into capsules,
Speaker 6: and these capsules can be taken by the patient at
Speaker 6: their doctor's office, and the patients are observed for several
Speaker 6: hours afterwards, and then they can usually start eating four
Speaker 6: to six hours afterwards as well. And then in many cases,
Speaker 6: patients are discharged on the same day so they're able
Speaker 6: to go home. And you know, one thing we are
Speaker 6: really keen on emphasizing it open biome is prevention of
Speaker 6: cediff when patients go home, you know, making sure that
Speaker 6: their home is clean, making sure that high touch surfaces
Speaker 6: are cleaned so that they're not re exposing themselves to seediff,
Speaker 6: and you know where possible, avoiding antibiotics as well, or
Speaker 6: having a conversation with their physician that they've had an
Speaker 6: FMT might be at risk of sediff. So yeah, you know,
Speaker 6: the treatment itself is surprisingly straightforward in many ways, but
Speaker 6: I think the complexity is around the donus screening and
Speaker 6: making sure that the patient is appropriately selected for an
Speaker 6: FMT and that the risks and benefits are clearly communicated
Speaker 6: to them as well before performing the treatment.
Speaker 3: Gotcha, Yeah, that is fascinating. I love the idea of
Speaker 3: pills just like a little capsule of and here's a
Speaker 3: new microbiome for your gut. Like that's it just feels
Speaker 3: like the future. And so that actually your last comment
Speaker 3: there leads me to my next question, which is about eligibility.
Speaker 3: As you mentioned, unfortunately, not everyone who has a C.
Speaker 3: Deficile infection is eligible for an FMT, So I wanted
Speaker 3: to ask what are the criteria for eligibility and who
Speaker 3: decides it.
Speaker 6: So FMT is recommended for patients with C deficile that
Speaker 6: haven't responded to antibiotic therapy, and that's the only patient
Speaker 6: group that this treatment is recommended for at the moment.
Speaker 6: And so, you know, four hundred and sixty thousand Americans
Speaker 6: experience C deficile every year. Of those, about twenty to
Speaker 6: thirty five percent of film will experience a recurrence of
Speaker 6: that infection. And then potentially, you know, from that population,
Speaker 6: about forty to sixty percent will experience a second recurrence.
Speaker 6: And it's on that second recurrence of their C. Deficile
Speaker 6: infection that they are eligible for in FMT. The other
Speaker 6: consideration is, you know, FMT is still an investigational drug,
Speaker 6: and what that means is that it has not gone
Speaker 6: through the FDA approval process. And there remains some unknowns
Speaker 6: about the treatment itself, and so at this stage, in
Speaker 6: a relatively early time in the field, it's important to
Speaker 6: make sure that patients, especially those who are immunocompromised, for example,
Speaker 6: children or you know, those in pregnancy perhaps are carefully
Speaker 6: considered for FMT. And in some patients they may not
Speaker 6: be eligible because of perhaps one of those reasons that
Speaker 6: mean the risk benefit of that FMT treatment doesn't make
Speaker 6: sense in their case. So, you know, those are the
Speaker 6: main criteria really for an FMT, and I think over
Speaker 6: time we'll be refining those, hopefully both to enhance the
Speaker 6: safety of the treatment and also to improve the efficacy
Speaker 6: as well of each treatment that's administered.
Speaker 3: Yeah, and so you know, you mentioned that there are
Speaker 3: some risks associated with fmts, both short term and potentially
Speaker 3: long term. For instance, there's a lot that we still
Speaker 3: don't know about how our gut microbiota affect are risk
Speaker 3: of developing some chronic conditions, right like cancer, diabetes, heart disease.
Speaker 3: I mean, many studies have shown a link, but what
Speaker 3: that link actually means is that correlative, is it causative?
Speaker 3: It's unclear, And so could you walk us through some
Speaker 3: of the risks of FMT, both short and long term,
Speaker 3: or maybe what you see as the biggest gaps in
Speaker 3: knowledge regarding risk.
Speaker 6: Yeah, absolutely, so, I think when it comes to risk
Speaker 6: of FFT, you know, it's always quite concept specific. You know,
Speaker 6: in the case of c dificile infection, especially severe disease,
Speaker 6: which carries a very high mortality rate, and where even
Speaker 6: surgery carries a significant rate of morbidity and poor outcomes
Speaker 6: following the surgery, that profile, the risk benefit profile in
Speaker 6: that patient may be very different to someone who is
Speaker 6: very early in their seedff and perhaps has more options
Speaker 6: left on the table, such as antibiotics or BES, tuximab
Speaker 6: or other interventions. So I think the first thing to
Speaker 6: emphasize is that it's very context specific and depends on
Speaker 6: the patient. But more generally speaking, this is a treatment
Speaker 6: that relies on instilling bacteria into a patient. And we
Speaker 6: do all we can, you know, just like a blood
Speaker 6: transfusion to screen out pathogens and bacteria viruses, but you know,
Speaker 6: there is always the potential risk that an infection might
Speaker 6: be transmitted, and you know, COVID has taught us that,
Speaker 6: if you know, we have to continuously be evolving our
Speaker 6: criteria for screening for infections to you assess for new
Speaker 6: infections that might be on the horizon, especially antibiotic resistant ones,
Speaker 6: and also, you know, continuously enhancing the tests that we
Speaker 6: use to screen out pathogens that might be potentially transmitted
Speaker 6: in stall. The second sort of category of risks i'd say,
Speaker 6: are as you said, the potential association with non inf
Speaker 6: anxious diseases. To date, we haven't seen any evidence to
Speaker 6: suggest that FMT transmits any of those conditions or increases
Speaker 6: the risk of those However, I think it's something that
Speaker 6: we have to be very mindful of that we don't
Speaker 6: have much evidence on the long term effects of FMT,
Speaker 6: and so it's really important you know, with the patient
Speaker 6: that the clinician is having a meaningful conversation around the
Speaker 6: risks and the unknowns of some of these long term
Speaker 6: consequences of FMT. But you know, for a patient who
Speaker 6: has run out of all of their treatment options and
Speaker 6: faces potentially resection of their bowel or long term antibiotics,
Speaker 6: or you know, even worse development of really severe disease,
Speaker 6: that sort of risk benefit needs to be taken into consideration.
Speaker 6: You know, there are sort of efforts being made to
Speaker 6: set up registries. So the American College of Gastroentrology has
Speaker 6: set up a patient registry to all the recipients of
Speaker 6: FMT to ten years. And I think that's going to
Speaker 6: be really helpful in understanding the risk profile of FMT
Speaker 6: and also the long term curates as well.
Speaker 3: Yes, absolutely, And so you mentioned that this is still
Speaker 3: pretty new and those early studies. When I talk about
Speaker 3: the early studies of FMT, we're talking less than ten
Speaker 3: years ago, and you know, those did show incredible effectiveness
Speaker 3: in curing C. Difficile infection. Has that success been maintained
Speaker 3: since those early studies and as the number of fmts
Speaker 3: performed has increased.
Speaker 4: Over the years.
Speaker 6: Yeah, that's been the really interesting thing. So you know,
Speaker 6: at open Biome we follow the clinical outcomes of each
Speaker 6: patient that receives an FMT. A few years ago, we
Speaker 6: presented data on over two thousand patients who had received
Speaker 6: an open Biome treatment and observed a clinical curate of
Speaker 6: eighty two percent, which is pretty consistent with the findings
Speaker 6: in clinical trials. But also the American College of Gastoroentrology
Speaker 6: or ACG, have been running a patient registry as well
Speaker 6: that I mentioned, and they've to date followed up two
Speaker 6: hundred and fifty nine patients and observed clinical curates of
Speaker 6: ninety percent. And so, you know, we're seeing these findings
Speaker 6: from these randomized control trials being replicated in the real
Speaker 6: world setting, which is very reassuring for the treatment and
Speaker 6: its use in clinical practice. But I think what we
Speaker 6: are going to hopefully learn more about in the coming
Speaker 6: years is how to improve that efficacy, how to select
Speaker 6: patients so that we are using this in the right
Speaker 6: context and the patient's microbiome perhaps is suited to this treatment.
Speaker 6: I think also, you know, simple questions like dosing for example,
Speaker 6: could be potentially optimzed. And so we're still learning so
Speaker 6: much about you know, what it is that leads to
Speaker 6: a clinical cure, why is it that some patients don't respond?
Speaker 6: And you know, hopefully we're going to be gathering more
Speaker 6: data on you know, the real world evidence over time.
Speaker 4: Yeah.
Speaker 3: Yeah, that's that's really interesting. Those are incredibly high cure rates.
Speaker 3: That's it's just an amazing it's just an amazing thing.
Speaker 3: And for this amazing, potentially amazing life saving treatment, there
Speaker 3: have got to be I assume some barriers in terms
Speaker 3: of cost or access. So what are some of those barriers?
Speaker 6: So, yeah, at open Biome, you know, our goal is
Speaker 6: to reduce the costs of treatment so that patients can
Speaker 6: access this at their nearest hospital. And so we've got
Speaker 6: over a thousand hospitals now that are able to provide
Speaker 6: open treatments. And the way that we've reduced the cost
Speaker 6: of treatment is by centralizing all of that. Don't is screening.
Speaker 6: You know, if only three percent of donors pass the
Speaker 6: clinical screening, you can imagine that a ninety seven percent
Speaker 6: of that for a clinician to be able to screen
Speaker 6: donors who may not be eligible is really extensive. And
Speaker 6: so you know if for a clinician to do this
Speaker 6: themselves can range from four thousand to up to twenty
Speaker 6: thousand dollars per single treatment in an open by and
Speaker 6: we charged just over two thousand dollars for our treatments,
Speaker 6: and so that hopefully makes the treatment itself more accessible.
Speaker 6: But FMT today is still an investigational drug, so it
Speaker 6: hasn't received an approval from the FDA. It's being provided
Speaker 6: to patients under a framework called enforcement discretion. What does
Speaker 6: that mean to this question? It means that the treatment
Speaker 6: itself at the moment isn't covered by insurance, and so
Speaker 6: patients are having to pay out of pocket for it
Speaker 6: or altensively. You know, the clinicians are having to eat
Speaker 6: up the cost themselves, and so that obviously creates a
Speaker 6: barrier to access as especially if we're thinking about coverage
Speaker 6: in some of the more rural areas or centers that
Speaker 6: might not be near a large gastrotrologists or infectious disease practice.
Speaker 6: But you know, I think an interesting other lens on
Speaker 6: this is that, given we are still quite early in
Speaker 6: the field, is there some justification for potentially building up
Speaker 6: centers of excellence that can provide this treatment At their
Speaker 6: centers do all of the really sort of rigorous screening
Speaker 6: and assessment of the patient and follow up and really
Speaker 6: you know, gathering the data to understand how effective this
Speaker 6: treatment is.
Speaker 3: Right, Yeah, So in this episode so far, we've largely
Speaker 3: been focusing on fmts in the context of clostridium deficile,
Speaker 3: but they have been found to be an effective treatment
Speaker 3: for a number of other conditions, or at least there's
Speaker 3: been early explorative research looking at fmts for other conditions.
Speaker 3: So can you take us through some of the research
Speaker 3: that open Biome is working on in terms of other
Speaker 3: applications of FMT beyond ce diff infections.
Speaker 6: Yeah, sure thing. So I think one example that's really
Speaker 6: interesting and potentially points us to how the field might
Speaker 6: move in the future is a clinical trial that we
Speaker 6: did looking at fecal transplants in hepatica and caphilopathy. So,
Speaker 6: hepatica cathelopathy is a condition that is associated with late
Speaker 6: stage liver disease liver cirrhosis, and it is characterized by
Speaker 6: confusion and agitation, drowsiness, loss of consciousness, and can be
Speaker 6: you know, putting patients into the intensive care unit and
Speaker 6: is typically quite a challenging condition to treat, especially to
Speaker 6: maintain clinical cure. But it's caused by a build up
Speaker 6: of nitrogenous waste products that you know, accumulating the systemic
Speaker 6: circulation and part of the role of the gut bacterias
Speaker 6: to break down some of those waste products. And so,
Speaker 6: working with a colleague of others, doctor Chaz Bagage at
Speaker 6: University of Virginia, we conducted a randomized control trial that
Speaker 6: showed that FMT was able to effectively treat this Basically
Speaker 6: in this trial of about twenty vations so a small study,
Speaker 6: half of the patients in standard of care group were
Speaker 6: cured and all of the patients in the FMT arm
Speaker 6: had a clinical cure. And so that's just a really
Speaker 6: interesting sort of example of you know, we talk about
Speaker 6: the gut brain axis, and you know, this is sort
Speaker 6: of an early example of how potentially FMT and the
Speaker 6: gut microbiome may play a role in that. The other
Speaker 6: piece of the study that I think is really interesting
Speaker 6: is doctor Bajaj characterized the gut microbiomes of these patients
Speaker 6: before the study to see whether there were some common
Speaker 6: microbial signatures in the composition or function of the microbiomes
Speaker 6: and these patients. And you know, we observed that these
Speaker 6: patients were particularly depleted in bacteria that play a role
Speaker 6: in the production of short chain fatty acids. And so
Speaker 6: what we did was to go back to our donors
Speaker 6: and we characterized the microbians of our donors and selected
Speaker 6: a donor that had a particularly high abundance of these
Speaker 6: microbes that these patients were depleted in. And so, you know,
Speaker 6: that sort of rational donor selection or personalized medicine approach
Speaker 6: to this maybe something that we see more and more
Speaker 6: in the future. And you know with the sort of
Speaker 6: falling costs of genomics and the introduction of that into
Speaker 6: clinical practice, So I think that's a really interesting one.
Speaker 6: You know, the other diseases like inflammatory bowel disease, there've
Speaker 6: been a number of trials now that have shown promise
Speaker 6: in that, especially in alternative colitis, where you know, we're
Speaker 6: seeing in patients with this very difficult disease about thirty
Speaker 6: seven percent of patients are in clinical remission after a FMT,
Speaker 6: which compared to about eighteen to twenty percent for standard
Speaker 6: of care. Is really exciting. And then you know, as
Speaker 6: a nonprofit, we are also exploring the role of this
Speaker 6: in disease areas that are perhaps neglected by farmer companies
Speaker 6: in the US and Europe, to support clinical trials in
Speaker 6: lonand Lincoln Countries, and so we're actually working with the
Speaker 6: University of Kicktown at the moment looking at the role
Speaker 6: of fecal transplant in children with severe cute malnutrition who
Speaker 6: failed to respond to a nutritional therapy, which is surprisingly
Speaker 6: the case in about a third of kids with malnutrition.
Speaker 6: So yeah, really broad disease areas that we're working on.
Speaker 3: So that is so incredible though, that is I mean, yeah,
Speaker 3: like you said, very broad but promising, and it's just
Speaker 3: seems like such an incredible potential solution. So what do
Speaker 3: you see as the future of FMT. What hopes do
Speaker 3: you have for FMT in the future.
Speaker 6: Yeah, so, I think we are at such an early
Speaker 6: stage of our understanding of the microbiome and the potential
Speaker 6: and the way that we should be using FMT, And
Speaker 6: what I hope is a few things. I think firstly,
Speaker 6: that we've accumulated more and more data on patient outcomes
Speaker 6: in a more systematic way across the world for all
Speaker 6: patients that are receiving this treatment. I think the second
Speaker 6: pieces that aspect of personalization, and you know, can we
Speaker 6: do more to potentially increase the curates for patients who
Speaker 6: are receiving FMT for conditions like cediff And you know,
Speaker 6: perhaps in the future, you know, we're treating patients who
Speaker 6: have failed multiple rounds of antibiotics, But is there potentially
Speaker 6: more that we can do in prevention. Is there a world,
Speaker 6: you know, perhaps you know in a few years time
Speaker 6: where you bank your stool prior to receiving antibiotics and
Speaker 6: then you receive your own stool back to restore your
Speaker 6: gut microbiome after a course of antibiotics. This is already
Speaker 6: being explored in some patients, some patient populations who are
Speaker 6: receiving lots of antibiotics, like stem cell transplant patients. But
Speaker 6: we I think open Biome are really interested in a
Speaker 6: public health approach to FMT in the microbiome, and can
Speaker 6: we prevent diseases as much as treating them when patients
Speaker 6: are really sick? And you know, i'd say sort of.
Speaker 6: The last thing really is we started open Biome to
Speaker 6: enable access to this treatment for patients when they need it.
Speaker 6: We know that there's still much more to do for
Speaker 6: that in the US, but I think globally, SEEDIFF is
Speaker 6: likely to become more and more of a burden as
Speaker 6: we see wider antibiotic use and wider occurrence of risk
Speaker 6: factors they are associated with seed IFF, like inflammatory bowel disease,
Speaker 6: And so I think we're going to have to be
Speaker 6: really mindful of making sure that people who may not
Speaker 6: necessarily have access to the same health systems as we
Speaker 6: do in the US can still access this treatment when
Speaker 6: they need it. I think COVID has highlighted more than
Speaker 6: ever the importance of sort of health equity and technologies
Speaker 6: and access to them as quickly as possible, and so
Speaker 6: I think, yeah, hopefully that's the other piece that gets
Speaker 6: resolved and we're all working towards over time.
Speaker 3: Thank you so much, doctor Osmond. That was just so
Speaker 3: enlightening and I think I somehow I didn't know it
Speaker 3: was possible love fecal microbida transplants that much.
Speaker 2: More, even more, even more, Oh, Aeron, what a fun
Speaker 2: episode this was.
Speaker 3: This was very interesting. I mean it did have its
Speaker 3: frustrating moments. Yeah, like I.
Speaker 2: Really wish that we had better numbers, and yeah, there's
Speaker 2: a lot of frustrations.
Speaker 3: But this was I mean, I think sea diiff is
Speaker 3: a very remarkable pathogen, and that it's not necessarily a pathogen,
Speaker 3: and its recent emergence and how much our existing medical
Speaker 3: structures kind of facilitate the growth of this bacterium and
Speaker 3: the spread of it is terrifying.
Speaker 4: Absolutely.
Speaker 3: Yeah. Well, okay, should we do sources? Yeah, let's okay.
Speaker 3: So I'm just going to shout out a few. I
Speaker 3: have a bunch of papers, but a couple that were
Speaker 3: key for the history and genomic aspects of sea diff.
Speaker 3: One is by Bartlett from two thousand and eight. And
Speaker 3: the other is the one that I already mentioned by
Speaker 3: night at All from twenty fifteen. And then in terms
Speaker 3: of the fecal microbide of transplant stuff, I contain multitudos
Speaker 3: by Edyong, a very fun book about the human microbiome.
Speaker 3: Check it out, and by de Groot at All from
Speaker 3: twenty seventeen. And I have to shout this out also
Speaker 3: because it doesn't just have great information, but it also
Speaker 3: contains and amazing figure. One of my favorite that I've
Speaker 3: seen of the most important developments in the timeline of
Speaker 3: fecal microbida transplants, but it's marked along intestines. It's starting
Speaker 3: in one part of the intestine going together. It's beautiful.
Speaker 4: Oh that's so cool.
Speaker 3: I loved it.
Speaker 4: Yeah.
Speaker 2: One of my favorite papers that I read was actually
Speaker 2: it was by crowboch at All twenty eighteen called Understanding
Speaker 2: Clusterdium difficile Colonization. I found that one just really really interesting.
Speaker 2: But there was a number of other review papers on
Speaker 2: sort of seediff infection and a couple at least including
Speaker 2: the Global Burden of Clusterdium difficile Infections, A system review
Speaker 2: and meta analysis that we're trying to get at the
Speaker 2: global distribution. Yeah, so we'll post a list of all
Speaker 2: of those sources on our website, This podcast will Kill
Speaker 2: You dot Com under the episodes tab.
Speaker 3: Thanks again, Lany so much for providing the first hand account.
Speaker 3: We really appreciate you taking the time to chat with us.
Speaker 4: Yeah, thank you.
Speaker 2: Thank you also to Bloodmobile, who provides the music for
Speaker 2: this episode and all of our episodes.
Speaker 3: And thank you to exactly Right, of whom we are
Speaker 3: a very proud part.
Speaker 4: And thank you to you listeners.
Speaker 2: You make this podcast possible and we love you for it,
Speaker 2: we really do.
Speaker 3: Especially thanks also to our patrons. You guys are absolutely amazing.
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Speaker 3: joy it is. Okay, well, this feels quite relevant, but
Speaker 3: does until next time, wash your hands.
Speaker 2: You filthy animals, with soap and water and not just
Speaker 2: an alcohol based hand sanitizer.
Speaker 4: I like that.