The Poo Replacement Treatment – Faecal Microbiota Transplant

Interview with Dr. Nathan Connelly – Faecal Microbiota Transplant

Nick: Welcome to episode two of The Holy Gut Podcast. In this podcast we talk about FMT.

Hello. It’s Nick Kemp here, co-host of The Holy Gut Podcast with my co-hosts, Dr. Nathan Connelly and Nicole Starbuck-Connelly. Nathan is a gastroenterologist, and Nicole is a registered nurse and practice manager of the Moonee Valley Specialist Centre here in Melbourne, Australia. Moonee Valley Specialist Centre provides a number of services related to gut health, including FMT and bowel cancer screening.

Nick: Welcome back to the podcast, Nathan. Today we are discussing FMT, so would you like to start by explaining what that is?

Nathan: Thanks very much, Nick. FMT, or fecal microbiota transplant, is the replacement of someone’s bowel flora with a bowel flora from a so-called healthy person in order to benefit their health and especially to try and cure a disease.

Nick: I see. I actually read a newspaper article, and the title was … It had “poo swapping treatment” in the title. So I guess that kind of also helps make it clear that’s actually what the process is. You’re taking healthy poo, and I guess you’re putting it in the colon of someone else who has some trouble with their flora-

Nathan: Yes.

Nick: … and you’re coating the colon wall with healthy poo.

Nathan: Yes, it’s not a poo swapping in terms of I give you yours, and you give me mine . But it’s really a … Poo replacement would be a better word for it.

Nick: I see.

Nathan: You’re actually trying to engender a very significant change in the patient’s bowel flora.

Nick: What’s the theory or the evidence behind this treatment?

Nathan: The whole theory behind this treatment goes back over 2,000 years, and the first people to notice this where shepherds. Now, there’s various different theories on which shepherds it was. Some people think it was camel shepherds, other people it was sheep shepherds. But either way, they found that their animals, if they became sick, if they fed them stool orally from animals that were well, that the animals became well again. So it’s been known about for centuries. There’s reports of it through empirical sort of medical evidence going back centuries. It’s been used on and off by various medical practitioners before we had modern medicine

Nathan: But the basic theory behind it is that, one, that diseases are caused by changing bowel flora and, two, that you can effectively fix that by giving the patient back normal bowel flora. And the whole idea really around FMT is it’s a whole of bowel flora or a whole of stool approach. You’re not just giving one bacteria or two bacteria. You’re giving all the bacteria, as well as the stuff that’s in stool as well. Possibly yeast, possibly viruses, possibly … we don’t know. But just the whole of the stool is a benefit to health, but predominantly we think it’s due to the bacterial flora in the bowel.

Nick: I understand. In terms of modern medicine, I imagine it’s a fairly new treatment.
Nathan: Yeah. It’s a very important point, when you’re looking at FMT, every single indication for it is specific to that indication. So when you’re talking about evidence or when you’re talking about how you do it or how much you have or how long you have it for, it’s all specific to the medical problem you have. So I’ll give an example of three disorders to start with where there is actually good medical evidence for fecal microbiota transplant.

Nathan: The first one is Clostridium difficile infection, which is an infection that people get when they’re in hospital having antibiotics, and it’s a bacteria that makes them very sick. And often, you can treat this nasty infection with more antibiotics, but when you stop the antibiotics, it comes back. And the reason it keeps coming back is because the person doesn’t have any normal bowel flora. This is a condition that kills, I think, 2,000 people a year in the US. They’ve got a very bad form of CDF over there, and they used FMT in trials to prove that it would cure people. And a one-off FMT cure was 98% of people with Clostridium difficile infection.

Nick: I see. Gee, that’s-

Nathan: I’ve done a dozen or so of these, and they go into the procedure with diarrhea, and they wake up without it. It cures all of them. It’s been written up in the New England Journal of Medicine, which is one of the top five medical journals in the world. And it’s all done and dusted, sealed and delivered. It’s FDA approved in America. And that’s the one condition we have absolute unequivocal evidence for.

Nick: I see. That’s obviously very good news. A lot of people might find this procedure hard to understand or stomach, but if there’s evidence and-

Nathan: These patients are very sick, so often it’s a case of have it or die. The US, they’ve got very nasty Clostridium difficile infection. So it’s been revolutionary for that condition when it difficult to treat. Not all patients with CDF need it. Some patients or most patients, give them the antibiotics and stop the other antibiotics, and they get better anyway. So it’s only a small percentage that need it. But when you’ve had four courses of antibiotics, and it keeps coming back, you haven’t got any other choice.

The second condition is inflammatory bowel disease. And certainly in patients with ulcerative colitis, if they’re not responding to other treatments, a good percentage of the patients do respond to FMT, but you have to keep doing it because the bowel of people with ulcerative colitis is very sick, and therefore, the bacteria don’t want to live there either, so you have to keep pumping it in.

The latest study, which was actually done in Sydney, they did 40 transplants over an eight-week period, and approximately 40 to 50% of the patients got better. And we’re not talking about patients with mild ulcerative colitis. We’re talking about people with severe disease who might end up needing their bowel removed. So if you’ve run out of treatments for your ulcerative colitis, then the FMT is an alternative.

And the last one is autism, which isn’t a disease. Got nothing to do with the bowel at all, well, we didn’t think it did, but there’s some evidence that FMT will work for autism, which is interesting because there’s not much other else in the way of a directed treatment for the condition.

So each of these proven, if you like, indications, you do it differently for each three of them.

Nick: I see. With autism, autism has quite a spectrum where it can be mild to quite severe and debilitating. Are you treating people on any part of that spectrum?

Nathan: Yeah, I think that hasn’t been worked out. So the study, the initial study, which I think was done in Arizona, which is positive to a point, hasn’t done subgroup analysis or looked at which age group or when you should start or how severe you should be. We don’t know the answer to that question. So although there’s some initial studies in each condition showing potential for benefit, the exact subset groupings and the nuances haven’t been looked at. We could be doing FMT research for the next 50 years before we work it all out.

Nick: Okay.

Nathan: I think there’s 200 trials either being designed or ongoing with FMT in the United States. There’s a lot of interest in FMT. For example, with multiple sclerosis, there’s a trial going on in that in the US, but it’s only recruiting certain types of patients. And a lot of the patients I see have conditions where there’s no treatment available or they’ve run out of treatments, and there’s indications from small trials that the treatment’s beneficial, but the actual overwhelming evidence is not available, but they can’t wait for that. That’s going to take five or 10 years.

Nick: Okay, yeah. I recall you saying that you have patients who come from different countries like the States to get this treatment.

Nathan: That’s correct. In the states, the FDA has a lot more control over what the doctors do. And unless it’s for CDF, you can’t do it.

Nick: Okay. To give the audience some sort of idea about the process, what actually happens? If someone were to come in for a FNT treatment, what would they go through?

Nathan: Well, the first thing I do in patients is take a full history of their problem. I look at what treatments they’ve had, I look at what other treatment options they have. If I’m not sure of the diagnosis, I may suggest further testing. If I’m not sure they’ve had all the standard treatments, I might suggest they do that first. So it’s not just automatically you walk in, you get an

FMT. I look to see how educated the person is in regards to FMT, so what do they understand about it? I tell them about FMT. I am very honest about the lack of evidence in certain conditions, what evidence does exist in other conditions. We look at risks. And then we design a treatment regime for them.

Nathan: And that process is shorter for some people and longer for others. If you’ve got CDF the process is very short. I tell the patient, “You’ve failed four course of antibiotics, this is really your only option,” and it happens the next day pretty much. But for patients with something like ulcerative colitis or autism, it would be a bit of a longer process.

Nathan: And the actual process itself of doing it is very straight forward. All of mine are done initially with colonoscopies, so the patient has bowel preparation, we clean their bowel out, we put a tube into the bowel all the way around to the right-hand side, and we inject approximately 300 to 400 mL of multi-donor stool into the cecum. After that, the patients will often have a follow-up enema, anywhere between one follow-up enema and possibly 20 or 30 follow-up enemas depending on their clinical problem. And sometimes because of the lack of evidence for any particular … or lack of data, we make our sort of program up as we go along. But in general, most patients have anywhere between one and five enemas afterwards, and that’s just done in the rooms, a little tube that we put up the bottom without any bowel preparation or sedation or anything else.

Nick: Okay. You mentioned risks. What are the risks or what do sort of people need to be aware of?

Nathan: The risks are mostly theoretical. The risk would mostly center around the transmission of infectious disease. Despite the number of FMTs that’s been done worldwide and despite the fact that a lot of FMTs probably being done outside of medical supervision, so people doing it themselves, there’s been really relatively few reports of harm when doing it properly. So if you do it from the bottom end, and if you screen your donors for all the diseases you can, so they have blood tests for HIV, hepatitis C, hepatitis B, et cetera, you only use healthy donors of normal weight, and you test their stool for all the parasites and bacteria, then the procedure is extremely safe. And as I said, there’ve been no real reports of any harm with it being done colonoscopically or via enema.

Nathan: There were some issues when people were doing it from the top end of … Why they were doing it from the top, I’m not sure, but with a gastroscopy at least there’s the risk of aspirating the stool, and poo in your lung is not a good thing. So I’ve never done one from the top end, and I never would. But the bottom end, it’s probably extraordinarily safe.

Nick: I see. You mentioned donors, so obviously you screen the donors for their general health, and then obviously the health or, I guess, the flora quality of their poo?

Nathan: Yeah. The first point I guess is they’re all tested for all … First of all, we ask them a questionnaire. They’ve got to be healthy. We prefer vegans, not for any particular reason other than we think they’d probably have better bowel flora. They have more diverse bowel flora. And also, vegans are easier to get as donors, I think. They tend to be more community-minded, so they’re more affable donors. And they also tend to probably have better stool flora. We test them on questionnaire. We don’t like people who are too overweight. We don’t like people with any history of any illness whatsoever. We test them for all these illnesses. We test them for viruses and bacteria.

Nathan: Beyond that, though, what makes a good donor is unknown. There is some emerging data from these … You might remember the test I was mentioning yesterday, the r16 ribosomal subunit test or uBiome test as it’s known in America. That test is being used to try and work out who are good donors, and there certainly is mounting evidence that some people are good donors and some people are not good donors. But what makes a good donor is only being slowly worked out. In one of the trials with ulcerative colitis, it turned out that only one donor was any good. And the response rate for that donor’s stool was very high, and the response rate to everyone else’s was quite poor. But what exactly makes a good donor is unknown.

Nathan: For Clostridium difficile infection, the initial disease, it doesn’t matter what your donor’s like. You could have a terrible donor, and it doesn’t make any difference. So almost certainly what makes a good donor might even be specific to the disease you are using the FMT for.

Nick: I see. And you mentioned you’re actually taking multiple stools from multiple donors and mixing that.

Nathan: Yes. To try and remove that donor effect, if we can’t work out what makes a good donor, then just have lots of donors.

Nick: I see.

Nathan: Seems to make sense. With our patients, generally there’s three to five donors minimum.

Nick: I imagine the audience might want me to ask this question. How long does the donated stool or poo stay in the colon, like the first treatment?

Nathan: The vast majority of patients, you don’t know the answer because they might not use … For a colonoscopy, for example, they might not use their bowels for two days, and that’s normal after a colonoscopy. The amount of fluid you’re actually putting in, spread over the whole colon is actually quite small. We’ve had the occasional case of people who’ve had a bowel action that afternoon, and they do worry whether that means that they’re not gonna hold their FMT, but that hasn’t seemed to have been a common problem. It happens maybe one in every 50 cases. But the vast majority of patients have the same response as they normally have after colonoscopy, which is to not use their bowels for a day or two. The actual bacteria stay in there. The fluid and the fiber and the other stuff that’s found within the stool will come out as per usual, 24 to 48 hours after the procedure.

Nick: I see. Yeah, it’s quite an amazing treatment. And I think if you can get past the idea of the actual procedure, and it’s now verified, and it’s helping people with all these health problems, I guess it’s something people can consider.

Nathan: Yeah. I think you have to be a bit careful with overexuberance. And I think the major thing in doing any procedure or treatment or lifestyle change or anything with patients or people in general is just informing people what the evidence actually is. You see so many things written about bowel flora and FMT, and none of it’s referenced. The evidence for this or that is not spoken about. That doesn’t mean you shouldn’t do it. And as I said before, a lot of people can’t wait for the evidence to come out, and the trials will take years. And even within that, you’ve got to look at the way the trial is done, how they do their FMT, do they use multi-donor, do they do enough of it, do they choose the right subset of patients.

Nathan: And I think if the patient’s informed and is willing to accept the very small risks, as well as the uncertainty, that you shouldn’t deny them the treatment either. Because I think what’ll happen is people will just go and do unsupervised FMT. So they’ll use a donor that’s not appropriate, or a donor that hasn’t been screened, or they won’t do it the right way, and that might lead to problems, and hence people will start getting worried about FMT. So I think you got to have a balance between needing evidence and acknowledging that you can do it without evidence because what people don’t realize about medicine is a lot of the stuff we do doesn’t have evidence.

Nick: All right, well, this has been very insightful. I believe we’re doing a three-part series on this, so in part two I’ll be speaking to your wife, Nicole, about donors, and in part three we might go into more detail about people’s seeking this treatment. So thank you for your time, Nathan.

Nathan: It’s my pleasure.

Nick: And we’ll probably speak on another podcast soon.

Nathan: Thanks, Nick.

Nick: Thank you.

This episode of The Holy Gut Podcast was sponsored by the Moonee Valley Specialist Centre. For more information about Nathan and Nicole, please visit mvscentre.com.au. If you have any questions related to gut health that you would like answered on the podcast, please let us know via the contact form at mvscentre.com.au.

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