FMT Therapy For Autism

 

Nick: We are back speaking to Nathan about FMT for autism. So, Nathan, why the interest or why the belief that FMT can help autism?

Nathan: Look, it’s a very interesting question because obviously most people consider autism to be a brain disorder, and I won’t go into what autism is. I assume the listeners have some basic understanding of the condition, but for quite a while there’s been some lines of evidence that autism does relate in some way to disorders within the gut.

Nathan: The first level of evidence really is that autistic children often, or nearly universally, have gut symptoms such as diarrhea, abdominal pain, bloating, constipation, et cetera, and at the severity of those gut symptoms seem to mirror the severity of the autism. That was sort of the first clue.

The second clue is that there is a fair bit of evidence that antibiotic therapy, what we call intestinal decontamination, does help some children with autism. And thereafter there have been some studies done specifically on FMT looking into whether it could help children with autism.

There also have been some studies looking at changes in natural bowel flora. Since we’ve had these very sophisticated DNA-based tests of bowel flora integrity, if you like, it’s fairly clear that children with autism have decreased bacterial diversity, meaning that the number of different kinds of bacteria reduce. That’s been pretty clear from most of the studies into bowel flora changes in autism.

Nick: Okay. So there’s a lack of a diversified gut flora in children with autism.

Nathan: Yes, that’s true.

Nick: And so what FMT offers is this flora they can’t produce or just don’t have in their gut and bowel.

Nathan: That’s right.

Nick: And so the theory being, if they’re supplied with that flora, it should help their gut function probably, which should then also help their behavior, their overall health and, I guess, their brain?

Nathan: Correct. Improve these symptoms of autism.

Nick: There’s something I came across in doing the research for this podcast, and that was the gut brain axis. So do you want to touch on what that means?

Nathan: It’s an impracticality. The kilo or so of bacteria within predominantly your colon, because they’re all supposed to live in your large bowel, these bacteria are metabolically active, so they’re metabolically active in many ways.

Firstly they do make things, so they turn your food residue, stuff that you don’t absorb, into substances, for example, hydrogen sulfide, methane, opiate type substances and a whole bunch of other things. Butyric acid, propionic acid. So some of these substances may be good for people, some of these substances might be not so good for people. So they’re metabolically active.

Secondarily they interact with the gut immune system, and their interaction with the gut immune system within what’s called the mucus layer, which is the very thin layer of slime, if you like, over the top of your bowel mucosa, it’s full of bacteria and it’s full of immune cells and there’s an interaction between the immune system and the gut flora, and that also causes changes in what’s called the gut barrier or mucosal barrier which can be breached and which can cause the entry of bacteria and bacterial products into the circulation.

So this is very interesting interaction, which still hasn’t been worked out to anywhere near the degree that we need to between the bowel flora and the integrity of the gut wall and the activity of the gut immune system. And that in turn, those bacterial products, that interaction with the immune system, the integrity of the gut lining, is thought to cause changes within the brain.

And there’s all sorts of diseases that have been looked at. Autoimmune disorders like multiple sclerosis, degenerative disorders like Alzheimer’s and Parkinson’s disease and other diseases like autism. Mental health issues like depression and anxiety. All of these are being studied in terms of what effect bowel flora changes might have on those disease. So that, if you like, is your gut brain axis.

Nick: I see. Okay. Now that you’ve mentioned studies, I think what I’ve read is, and what you sort of just mentioned, is that FMT seems to help children with autism and help obviously maybe their brain functioning and their behavior. But at this stage, the reasons why that’s happening haven’t come to light. So it’s working, but you sort of don’t know why.

Nathan: That’s true of most … I don’t want to say most. That’s true of a lot of things in medicine, Nick. We often put the therapy before the mechanism and that’s been the case for years. There’s a history of that in medicine that goes back centuries. We don’t know always why our medications work and we don’t really know why FMT works in autism.

As I’ve mentioned in previous podcasts, the whole thing with FMT and any condition, the proof for FMT has to come with every single individual condition. You can’t generalize. So with most conditions that have been linked to improvement in FMT, the evidence exists only in terms of a theoretical basis or from very small series of cases. I did 10 cases, I did five cases, I did one case, we do a case report, stick it in a journal, that’s not evidence that FMT works. It’s low level evidence, if you like.

So the search is always on in this space for better more robust evidence that this will work, and that evidence is being accumulated with FMT and a whole bunch of conditions. For example, we know FMT works for Clostridium Difficile Infection. We have class A evidence for that. It’s part of protocols. It’s approved by the FDA. It was published in the New England Journal of Medicine, and it’s well accepted if you have recurrent Clostridium Difficile Infection, you will get better with FMT. It is the gold standard treatment. There’s evidence in ulcerative colitis. It’s pretty overwhelming that it does help some patients with ulcerative colitis.

Nathan: So they’re two conditions where we have sort of class A evidence. Everything else up until recently has been either wishful thinking or has only a low level evidence for its use.

Nick: Okay. But obviously there’s been enough evidence for the FDA to fast-track status to the FMT, or Microbiota Transfer Therapy is what they call it.

Nathan: Yeah. Thank you for educating me on that. I hadn’t realized they had fast-tracked that, which is kind of extraordinary based on the history of FDA. They must be feeling a little bit guilty about restricting access to this treatment in the US when they come out so quickly and approve that because, as we’ll discuss in a minute, the evidence from the studies that have been done isn’t overwhelming. It’s not class A evidence. Nowhere near it. It’s highly criticizable research, to be honest. Not that I’m criticizing [inaudible 00:07:21] fast-track it because I think it’s incredibly safe therapies. I don’t have a problem with that. I just think the evidence is not particularly overwhelming. But I do think it works.

You’ve got to understand that the way the scientific brain thinks in medicine is even though you think something works, you have to still evaluate the evidence critically. You’ve got to be always scientific. You’ve got to have your scientific hat on.

I see. But in terms of this type of treatment, I guess it’s a safer treatment than giving child lots of medication to try and handle a condition that really people don’t know how to cure or manage.

Nathan: There’s no therapy for autism. It’s all supportive treatment. Don’t get me wrong, the supportive treatments have been transformative in autism. Before the supportive treatments, these kids had no hope. You know, probably put in a corner, told they were naughty, all the rest of it. But the treatments that we’ve had so far are in the end supportive.

So the most important part of treatment of autism really is the educational outcomes and trying to get the kids as functional as you can. So a lot of people have put a lot of time and effort and continue to in supporting families with autism. Not just supporting the child with special teachers and special education programs, but also supporting the family as well so that the family unit can continue to do well in the presence of an autistic child.

So, don’t get me wrong, those supportive approaches are absolutely vital and will continue to be vital even in the age of FMT. Likewise, sometimes, unfortunately medication does need to be used to modify behavior, although it really is only supportive. There is no medication known to treat autism. There are lots of things that have been looked at and suggested and there’s lots of stuff in the alternative medical field about autism, but there’s no proven therapy for autism.

Nick: Sure. Okay.

Nathan: So that’s right. So when you’re doing FMT for an autistic child, you’re not doing it and not giving them the right treatment, you’re just giving them a treatment, because there is no other treatment. All the others is supportive.

Nick: With the spectrum of autism going from mild to extreme, are the case studies being done on that spectrum?

Nathan: The published research is the Arizona Autism Group, which is in Phoenix, Arizona. Obviously they [inaudible 00:09:47] specialize in autism. My understanding, and to be honest with you, I haven’t recently read the whole trial, but my understanding is there was definitely a spectrum of cases. My understanding was the trial wasn’t double-blinded or sham-blinded, but the results were fairly robust in terms of the amount of response they saw, and they published follow-up data suggesting the response is robust and it does persist.

So even when you stop doing the FMT, they continue to have ongoing improvement just by the fact you’ve stopped, suggesting that the bowel flora is permanently changed. So it’s not something you have to keep doing all the time. And these children, the benefit is persistent.

Nick: With that in mind and perhaps now that it’s been approved or fast-tracked by the FDA, there’d be a lot of interest, especially with parents who are desperate to help their children. What could they expect from a treatment?

Nathan: I suspect like everything else, Nick, it’s going to depend on a whole range of factors, not just the FMT. So the FMT [inaudible 00:10:53] factors you can control. You can control is donor selection, you can control using multi-donor stool. We don’t know whether that’s important in autistic children or not because it hasn’t been studied. You can control pretreatment with antibiotics, you can control how long you do it for or how intensively you do it.

But there’s a whole bunch of factors you can’t control. I think one of the factors is how sick the child is. So it might well be that sicker children respond better, or milder children respond better. It might be that it’s best done earlier in life rather than later in life. We don’t know the facts around that. Hasn’t been studied.

This is one of the problems again with FMT is that not only have you got to work out whether it works, you’ve got to work out which group it works in best and how to do it best in a particular subgroup. So all of those questions have not been answered. It might work really well in mild disease but not really well in severe disease. It might be vice versa. It might be better if you start early, better if you start later. We just don’t know.

So therefore I think in an individual person sitting in front of me, I would suggest they have FMT and we see what happens. That’s as scientific as I would get with a patient in front of me. Let’s do it. See what happens.

Nick: Obviously we want to be honest about this. We’re offering hope and the possibility of improvement and it’s sort of a low risk treatment.

Nathan: What you’re doing is offering a still somewhat experimental but essentially safe, because there’s only been a couple of case reports recently of harm, but honestly I think the donors were poorly selected in that case and I think the patients were very, very sick.

So in general, there’s been hundreds of thousands probably of FMTs performed and there’s only one case report of harm occurring. So honestly I think it’s a very safe procedure. So you can offer a safe procedure that’s non-drug-based, which some patients like. I don’t have such a problem with drugs, but some people do. That is given for a condition that has no known treatment, or no proven treatment, that causes a significant loss of quality of life for both the child and also the family and which has some evidence for it. So it’s all winning all round. So it’s thumbs up for at least trying it.

What would be ideal, of course, is if a local program, a local autistic program would take this up, which is the appropriate setting in which it should be done. But unfortunately to get that ball rolling is very difficult for a large unit at a public hospital or children’s public hospital to say, well, we’re going to do a hundred and see what happens. That’s what needs to happen. They need to do their own program and their own research. That would be ideal. There’s enough there. There’s enough evidence accumulated to go right, some big public hospital should just do it and just offer it to a hundred kids and just do a pilot study and publish all the research. That would be ideal. But I haven’t heard any rumors that that’s being done, which is frustrating. [inaudible 00:13:55] with no known treatment, and it’s common.

Nick: What about yourself? Have you treated children with autism with FMT?

Nathan: I’ve done one adolescent child with autism. I have another one who’s in the wings who’s younger, who we’re just evaluating at the moment. But that particular patient has done extremely well. His educational attendance, his behavior has significantly improved with his Fecal Microbiota Transplant therapy. He continues to receive maintenance therapy, because in discussion with his parents we’ve decided that’s the right thing to do. But he’s now on three monthly. I think he has them once every three months, and he continues to improve.

Nathan: Now you can argue till you’re blue in the face why that is, but I do put it down to the FMT.

Nick: Okay, well that’s obviously a very positive outcome.

Nathan: It has been. He was my first. I agreed to try [inaudible 00:14:54] this patient because he was older, so I think he was 16 or 17 at the time we did it. So he was almost an adult. And for that reason, it made it sort of a lot easier in terms of the way our practice runs to be able to offer that to him. So that’s why I did him first, and I said, well if this works, I’d like to do another five to see what happens with the next five. I’m happy to extend that to younger children.

There are issues with an adult gastroenterologist doing FMC on younger children, but I think, as we’ve discussed previously, generally we do our first FMT via colonoscopy. I don’t think that’s necessarily necessary in autism. So doing barium enema with the parents involved in that therapy is pretty low-risk kind of thing to do.

Nick: All right. I know we have to wrap up soon, but I just want to go back to one more question regarding what the FDA has approved. So they’ve approved microbiota transfer therapy and full spectrum microbiota. So are they both FMT treatments?

Nathan: Yeah, so basically what you’re looking at is the whole lot, the whole box and dice, the whole house plus the people in it kind of therapy, which is what we do. There’s no processing of our FMT apart from mixing it up and sticking some saline in or some salty water in it. That’s all we do to it. But you can purify down. You can remove bits and pieces from the FMT and that would be your full spectrum.

Nathan: So your full spectrum would be the actual fecal matter removed from the FMT. It would be just the bacteria I presume is what they’re talking about.

Nathan: The full spectrum, so this is the whole point again of FMT versus probiotic therapy. People say why don’t you just take lactobacillus and do that? The problem is lactobacillus don’t do anything on their own. Even multi-strain probiotics haven’t shown any benefits. So we don’t understand.

Nathan: Everyone listening to the podcast has to understand we do not know why this works. You can presume all you like why it works, but we don’t know why it works. Therefore what we do know that works is just straight out FMT. Take some stool, mix it with some water, put it up there. That’s how we do it and that’s what works, so, therefore, that’s the way we do it.

Nathan: If you want to extrapolate that to other therapies based on that, then you can choose to do that, but it might not work.

Nick: I see. I do know you guys go to great lengths to screen your donors. You choose mostly vegan donors and you do a mix, don’t you?

Nathan: Yeah, so in some of the studies, I mean, for [inaudible 00:17:37] doesn’t matter. For colitis, it does appear that multi-donor is better, so we’re pretty keen on multi-donor. And we’re keen on vegans because they just tend to have better bowel flora. They tend to have more diverse bowel flora and more of the good kind of bacteria, I guess.

Nathan: Again, the evidence for that is not great. Certainly, you could get a whole bunch of people that eat McDonald’s every day and they could be very effective FMT donors, so we just don’t know. But we just think if you can be selective, you should try and select what you think is going to be the healthiest donor. And we would use at least three or four donors for every FMT, sometimes more.

Nathan: So I think there’s definitely some evidence in some conditions. That’s the case. And if you’re going to FMT someone, which is a pretty drastic thing to have done to you, I guess, you want to give it the best chance to work. So if it doesn’t work, it hasn’t failed because you’ve not done it properly. It’s failed because it’s just not going to work.

Nathan: And that’s what we want. We want you, you’re desperate, you’ve got no other treatment, you’ve got no other treatment options. We’ll do FMT, but let’s do the best possible FMT we can.

Nick: Right. Okay. So to wrap up, you believe it works, FMT for autism, and obviously you’re happy to help a family who is considering this treatment.

Nathan: Absolutely. If you look at the ethics around it, I think it’s unethical not to offer it, because there is evidence for its benefit and basically the condition has no other treatment.

If there was a proven therapy that worked and we’re doing it in exclusion of that, then that becomes ethically difficult because the evidence is not, as I said, it’s not class A overwhelming evidence, it’s just reasonably strong evidence. But that’s not the case in autism. There is no disease modifying therapy. There is all this supportive care, which again I will stress is absolutely vitally important and it’s vitally important that if you have FMT or if you don’t have FMT. And in no way am I at all advocating that that’s not going to be necessary or that that’s not still the gold standard treatment. What I’m saying is to modify the disease itself or to modify the underlying processes, there is no proven therapy. So yeah, I think in that situation, given the devastating impact it has, I think it’s unethical not to offer it should it be sought out.

Nick: I agree. I’ve got a few friends who have children, and it is hard to see how they have to handle it every day.

Nathan: Yeah. You see the children with autism, and everyone’s seen children with autism. There is a basic breakdown of the normal parental child relationship, which is heartbreaking. I find it heartbreaking to watch, I really do. And for that reason I really wish, I really do wish, and here’s a call to arms, if you like, or a bit of a poke. I really do hope that some children’s hospital somewhere in Australia gets together a program for doing FMT for autistic children, because it really should be done ideally in a multidisciplinary clinic with psychologists and researchers and microbiologists and all that kind of stuff that they can throw at it to try and work out how it works, why it works, what the best protocol is for the FMT, how to safely do it, how to less and how much you have to do, all those little details. It would be so fantastic to work out in such a rich vein of research for us to do. I really do hope they do it.

Nick: Yeah, so let’s hope that happens, and I know you’ve got to go, so thank you very much for your time today, Nathan.

Nathan: My pleasure, Nick. Thank you for asking me.

Nick: No worries.

The Moonee Valley Specialist Centre Faecal Microbiota Transplant Program

Hello, it’s Nick Kemp here, co-host of The Holy Gut podcast with my cohosts 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.

Hi Jody and Nicole, today we’re back and we’re going to talk about the FMT program in detail and in particular how you look after patients, both local and those who travel from overseas.

So Jody, as you manage the FMT program, do you want to give us a little bit of background about yourself?

Jody: Sure. I joined Moonee Valley Specialist Centre approximately two years ago, two – three years ago. When I joined my role was administration, and since then I’ve sort of moved in to helping our practice manager, who is Nicole, and Dr. Connelly work on the FMT program. We’ve seen a very big interest over the last twelve – eighteen months, and I believe that is obviously people researching the internet, there have been a few programs on television regarding the FMT program. When I joined I really didn’t know a lot about it and found it quite interesting. The whole concept makes a lot of sense and quite often these patients have exhausted a lot of other avenues, whether it be through medicines, lifestyle, whatever, and they have now come to wanting FMT as a last resort. This is where once the patient makes contact with us, and this is where I get involved.

Nick: I see. So, if we talk about the patient or a prospect when they first contact you, what happens?

Jody: Probably about 80% of our patients make contact via email and the other 20 by phone. Nicole and I have designed a program where that initial contact, we have four attachments that get sent to these patients. We have an initial letter outlining our practice, our fees, what needs to be involved, where they need to come and have the appointment. Then we have an attachment that has the fees. We also have a brochure that just briefly outlines what FMT actually is and how it is done. Then we have an attachment which is an accommodation brochure, that generally will be for patients who are coming from overseas or out of state. So we sort of briefly cover everything, which answers quite a lot of their questions. And then once they review all those, then they will make contact for an appointment, and then I schedule an appointment with Dr. Connelly to answer any medical-based questions that we are not qualified to answer for them.

Nick: Okay. So if they are happy and they understand the procedure, and you’re being transparent about the fees and they are ready to make the next step, they come in and they see Nathan and [crosstalk 00:03:59] obviously during that consult he would go through that –

Jody: With that initial appointment, obviously with all new patients they coming to Moonee Valley Specialist Centre and sit with Dr. Connelly and have an appointment. With our overseas patients or out of state patients, obviously it’s a teleconference, it’s a Skype appointment.

Nick: Mm-hmm (affirmative)

Jody: But if they do go ahead and walk-in for that initial appointment, I try to get them to email all their medical history, any [inaudible 00:18:59] testing or any testing that they’ve had done. Because quite often a lot of these patients have an extensive medical history, so I try to have all of that information ready to go for Dr. Connelly on that initial appointment.

Nick: I see. I see. So after they’ve had the consult with Dr. Connelly, then what is the next step?

Jody: So, sometimes with that initial appointment it’s very straightforward and Dr. Connelly may decide, yep, they are a candidate for FMT –

Nick: Mm-hmm (affirmative)

Jody: We will then write up a plan, because it is all done on an individual basis, every person is different and we’re treating it for different things. If he does that plan, that thing comes to me. Sometimes with these patients he may want a little further testing done on different things.

Nick: Mm-hmm (affirmative)Jody: I might not have gone down that path yet, so he will decide what he needs to do and when he is ready and the patient is ready, it may take another couple of appointments before it even gets to that.

Nick: I see. And then, once everything is clear and ready to go, I think you mentioned you have a pre-FMT appointment?

Jody: Yes. Once he passes over that plan to me, from there, I liaise with the patient, so Dr. Connelly then is out of the picture for a little while. I liaise with the patient, we work out a date that will suit them, because some of these patients may be anywhere from a week to three weeks, the whole process.

Nick: I see.

Jody: Okay. So we work out a date that works for them, then we generate all of the paperwork, the quotes, all of the future appointments, so there is a little bit of paperwork involved and a little bit of consultation between me and the patient, getting it all in place ready for them to go.

Nick: Mm-hmm (affirmative)

Jody: Once we’ve done that, then we like them to have an appointment one week before they transplant –

Nick: Yes.

Jody: Just to go over any unanswered questions. It could be anything, a number of reasons. We give them a patient pack, we make up a patient pack which has all their paperwork, their future appointments, it has their bowel preparation. We go over post-transplant what may happen, what they might feel after the procedure, so that appointment the week before just clarifies any unanswered questions and puts the patient at ease so that they are ready to go.

Nick: So you really roadmap the whole process, and it’s not just one day we’re talking about, it’s almost a process of up to a year, which we’ll sort of touch on later.

Jody: Mm-hmm.

Nick: But after that pre-FMT appointment, obviously the next time you see the patient, it’s the day of the procedure, so let’s talk about that.

Jody: Yes. That’s right. So, the day of the procedure is obviously at a private hospital.

Nick: Mm-hmm.

Jody: Generally, by this time the patient fully understands what’s involved, what they have to do. They arrive at the hospital. The whole procedure takes three to four hours. It’s just a day procedure. It is done under an anesthetic so we do ask they have someone with them for 24 hours. They are generally not allowed to leave the hospital unless they do have someone with them.

Nick: Okay.

Jody: So, we do ask that, and yeah, the procedure itself takes probably about half an hour, but from admissions right through to leaving the hospital the process is about three – four hours for the patient.

Nick: And then, post-procedure, what is the patient likely to experience?

Jody: Post – three – four days, Nicole and I advise the patients, you know they may feel a little uncomfortable, possibly experience a bit of diarrhea, bloating, sometimes they get flu like symptoms. Not everyone experiences this, but we do point it out so they don’t freak out and think “Oh my god, what’s going on, what’s happening?” It’s all very normal. We’ve designed a little rescue pack and a little card that we give the patients. So it just puts them at ease, so if it’s a Saturday or Sunday and they are unable to get a hold of us, they know that this is very normal and it’s nothing out of the ordinary.

We do give all of our patients Nicole’s mobile number, as you’re aware she is our practice manager and our nurse so they always got someone to contact if they are very unsure as a last resort. But generally, post-transplant, we schedule that next appointment three – four days after anyway, so we see them very close to having the transplant.

Nick: Okay. So with that next appointment, is that when they start having their scheduled enemas?

Jody: Yes. That’s right. So post, three to four days, that will be when Dr. Connelly does the first enema. Not all patients have a lot of enemas, most patients go from anywhere to one enema up to fourteen enemas. That’s where it comes back to the plan that he has for each individual patient, and it depends on why he is doing that and what he is treating.

Nick: And then after that first procedure, scheduled enemas treatment, then your after care service sort of starts.

Jody: Yes. Post-that, with all that initial paperwork, we sit down and work out their next twelve month appointment. So we always have one post-op one week, one month, three months, six months and twelve months. That way we keep in touch with the patient even though they may be well and everything is going great, we still want to keep in touch and have some feedback and just see how they are going and that they just don’t drop off the face of the earth.

Nick: Okay. So you really do look after the patient and make sure that they are happy, and I guess you do this also for yourself, to learn more about the treatment and to make it a better procedure.

Jody: Absolutely. They’re always looking for ways to improve the procedure and anything, we’re open to any positive feedback from patients. So far, the feedback’s been amazing and wonderful, but we’re always open to any new suggestions, but I think we run a fairly, fairly good program at the moment.

Nick: With your program, I think it is important to touch on donors again. So let’s talk about your FMT  donors.

Jody: Mm-hmm (affirmative). With our donors, we do rely heavily on our donors, because if we don’t have donors, we obviously don’t have a program. Our donors, we try to source from social media avenues, I think Nichole tried to reach out to the Vegan society, or naturopaths, all those sort of healthy lifestyle areas.

Nick: Yes.

Jody: We do get interest, and we do get emails, and they are very heavily screened. They have to fill out a very extensive questionnaire. And the questionnaire is related to lifestyle, eating habits, medical background history. It goes in to everything. They answer that, Nicole, our practice manager and nurse, she reviews the questionnaire, and if it looks like it would be a possible donor, then we send them a pathology request slip, and they are heavily screened, they do a full blood screening and they do a stool screening. If that comes back all clear, then they are candidates to be donors.

Nick: And you actually pay them to, don’t you?

Jody: We do, our donors are all paid. And they’re paid on the day. Once they donate, at the end of the day, because quite often when we’re doing enemas it’s all mixed fresh on the day, and they are paid at the end of the day.

Nick: I think that’s important to point out is that you pull, well we’ll just call it poo, you’re pulling this quality poo from six – eight donors, and you mix it and, if we talked about it as a product or a medication, it’s, you’re trying to find the best quality medication for the procedure.

Jody: You probably have to talk to maybe Nicole about this, she might know a bit more than what I do, if you want to step in and talk about the quality of …

Nicole: I think that there’s not quite enough evidence to suggest whether one donor or ten donors is better, what we do know though is that we think that multiple donors give us more of a varied flora, so what we try to do as a basic minimum is have at least two donors. And as you can appreciate not everyone can donate every day, so we are in a situation where, as Jody said, we rely on the donors, we don’t want them to donate when they’re sick, and we want to make sure that we run a really good program so as a very bare minimum we make sure that we ask the donors to donate every single week, at least once a week, so they’re in to the habit of doing this.

Nicole: It allows us to also have a store of our frozen enemas if we do need to use those for any reason. And, all of our donors are, really, really healthy. And there is some, although limited, there is some evidence to suggest that vegetarian and vegan donors are actually better than meat eating donors. So we have one healthy meat eater, and all of the rest of our donors are actually vegan at the moment. And we have got a lot more interest in the program, so I think the bigger we get, we have to make sure that we have more donors, before we open the program up to more patients. I think that is where we at with running our program at the moment. So currently we’re accepting maybe one – two patients a week in to our program –

Nick: Yes.

Nicole: But we have quite a lot of capacity I think in the coming year or so to increase that program quite extensively.

Nick: That was actually a question I was going to ask is are you looking for donors?

Nicole: I think it’s important to note that we are always looking for donors because when you have a donor who goes and gets a tattoo or goes overseas to Thailand, Bali, countries like that, we end up with a situation where they can’t donate for at least three months when they come back. Plus they need to get screened, and every now and then we have a patient that comes back, gets screened, and they don’t pass the screening. So we’re left with a situation where, it’s our practice policy to treat those patients if they would like to be treated, and we treat them as our own patients, our donors.

Nick: Mm-hmm (affirmative)

Nicole: But, whether we use them again as donors is up to Dr. Connelly, and we do have conversations about this, and often we’ll wait up to six or twelve months to reuse that donor if one of their tests has come back questionable.

Nick: I see.

Nicole: Yeah, so it can be challenging. And that’s why I think it’s important that we always have a rotating door of donors, and we’re always open to new donors, even if we don’t particularly need them, and we tried an actual, like Jody was saying before, I’m keeping touch fairly frequently with the Vegan Society, on Facebook in particular and I think there is about twenty or thirty thousand members in that and so I have little conversations on there with them, I put posts up. They are very aware of the fact that I’m not vegan, but that I am looking for very healthy people, and I’ve had a very positive response. And I think we probably get one – two interested parties each week. And they’re not all appropriate, but we probably pick up one every two or three weeks at least. They join the program and it allows other people to have time off if they need to.

Nick: I understand. Okay. I think we have gone in to quite a lot of detail and provided some useful insight into your FMT program and your patient care and the time you take to screen donors. So I think we’ll end the podcast here. Jody and Nicole, thank you for your time today.

Nicole: Pleasure.

Jody: Thank you.

Nick: 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.

A Faecal Microbiota Transplant Case Study

FMT Case Study

In this episode of theHoly Gut Health podcast, we interview Rita with her daughter Tamar who came from the United States to have the FMT treatment. We discuss the health problems, the decision-making process she went through to decide to have the FMT treatment, her inital concerns, the experience of the procedure and more.

 

Nick: Welcome to episode three of The Holy Gut podcast. In this podcast, we will discuss the FMT program with Nicole, who is the practice manager of Moonee Valley Specialist Centre, Jody, who runs the FMT program, and Rita along with her daughter Tamar, who came all the way from the United States for the treatment.

Nick: 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: As mentioned in the introduction, I’m here with Nicole, the practice manager and owner of Moonee Valley Specialist Center, Jody, who manages the FMT program, and mother and daughter Rita and Tamar, who came all the way from the U.S. for the FMT treatment. Rita, you came over here for the treatment. Do you want to begin by telling us about your health problems?

Rita: Yes. I have multiple sclerosis, and my daughter Tamar heard something that this FMT works on people who have this disease. After telling me that, I did my own research a little bit. I read that this FMT, this gut problem, has a lot to do on many diseases, actually. I knew that I have a gut problem because I experience constipation, sometimes diarrhea, so I have this problem. So I said, “why not try this one,” because I’ve tried every single medicine on the market for MS. None of them worked on me.

Nick: I see. So you try lots of other treatments, lots of medication.

Rita: Lots of medications, which they had very bad side effects, and I want to try this one. At least I know that it’s not going to harm me.

Nick: Okay. I understand. So your daughter Tamar was really the driving force behind suggesting to you and maybe encouraging you to try FMT. Tamar, do you want to talk about how you stumbled across FMT?

Tamar: Sure. This was really the culmination of several years of research on my part. I had observed my mom try all of these different drugs that are available on the market, incredibly expensive drugs, and she used every single thing. She did all of the treatments that the doctors prescribed and recommended, and none of it seemed to be stopping the disease in any way, shape or form.

So I went to the Internet, essentially, and I started researching. I literally Googled cures for multiple sclerosis, and I stumbled upon a medical article that was published by an American scientist in one of the universities in California talking about the connection between multiple sclerosis and gut bacteria. They had done some research with rats or mice, and they had seen that there were differences in the gut bacteria of mice that had multiple sclerosis versus the mice that did not. But that research didn’t go anywhere. They basically published that article, and then there was nothing being done about it, which was really frustrating to me, at least in the United States.

Tamar: So then, that led me to do further research about multiple sclerosis and gut bacteria, and then I stumbled upon some further articles, a publication that came out of Sydney. It was basically, serendipitously it seems, three patients had gone in for gut treatment problems like constipation and whatnot, and their multiple sclerosis symptoms improved after that, after getting the FMT treatment, which then made me research further and further to see if that’s being offered.

Tamar: Then we found out that in the United States, the FDA has basically banned doctors from doing this procedure on anybody that does not have C. difficile. That is the only medical illness where that’s allowed, and none of these other illnesses that could benefit from it, the doctors can’t do anything about it. They are allowed to advise you on basically do it at home type of procedures. They can help you with that, but they can’t do the colonoscopy for you. They can’t do the enemas for you. All of the things that need to be done that you would hope would be the most effective, they’re not allowed to do in the United States.

Tamar: So then I started researching, where can we get this done? Where can we try this treatment? And then I stumbled upon another website, which was The Power of Poop or something like that, and they list a whole list of doctors throughout the world who do this treatment. Now, not everybody is allowed to do it for anything other than C. difficile. For example, Canada, the United States, those are all C. difficile. But in other countries such as Australia, the Moonee Valley Specialist Centre was listed as providing this treatment.

So then I started reading up. I went on their website. I talked to my mom about it. I said, “You know, let’s do our research. Let’s call up. Let’s see if maybe this is a trip that we should be taking.” Because it is pretty daunting, if you think about it, to take a 16-hour journey all the way from the U.S. to Melbourne. My mom is handicapped. She’s in a wheelchair. She needs a hoist. These are all big things, and we need to make sure that this is going to be worth it.

Tamar: We talked to the doctor, and he was great. He was fantastic. He said, “We will offer you this treatment. You’ve tried everything else. We shouldn’t be denying you this opportunity to see what happens with you, and we will make the effort to make sure you have your hoist so we can transfer you.” We’ll make sure the hospital that was used, that they are going to be able to accommodate my mom’s needs. That’s why we made the journey up here, or down here, I guess, and we don’t regret it. It’s been tough, but it’s been a great experience.

Nick: I see. So, if we summarize, in the States, you were at your wit’s end. You were very concerned about your mother. You were obviously spending a lot of money on medication. I think in Australia compared to the U.S., our medication is far more affordable, so I think you could have been spending hundreds of thousands of dollars on medication. And you heard about this treatment. It’s something you wanted to explore, but obviously, because of the FDA in America, doctors hands are tied. They can’t provide the treatment, so you explored whether or not you could do it outside the U.S., and you found that Australia was an option. And then you were willing to obviously invest the money and time to try the treatment.

Rita: May I say something?

Tamar: Yes.

Rita: Money is not the reason I came here, because I have insurance over there. I was not paying a dime for those medications.

Nick: I see.

Rita: But I can tell you how much that medication, the recent one that I was using, how much it costs. It’s $69,000.

Nick: What?

Rita: $69,000 for six months.

Nick: How can a treatment be that expensive? Gee, that’s …

Rita: That’s the U.S.

Nick: That’s crazy.

Tamar: Well, you’ve got insurance companies, pharmaceutical companies, the FDA. There is a lot of red tape, a lot of bureaucracy, a lot of moving parts happening there that make it difficult. There are phenomenal scientists and doctors there. Everybody wants to help patients. They want to do things, but when you’ve got all these different organizations money ends up being a huge factor, marketing drugs and whatnot. I wouldn’t be surprised if at some point if this were to be approved for illnesses other than C. difficile, that they are going to try to put it just in pill form so that they can charge a lot of money for a pill versus doing actually FMTs. I wouldn’t be surprised if that is what is approved and not the actual FMT process. It would be phenomenal if they can approve the FMT process, but who knows?

Nick: Okay. If we go back to the FMT procedure, when you first started reading about it, how did you both react to the idea of the procedure?

Tamar: There’s a definite weird and yuck factor to it, but [inaudible 00:09:50] the research …
Rita: I didn’t want to [inaudible 00:09:53].

Tamar: Yeah. In the beginning, my mom was very, very hesitant about the whole idea, especially if we didn’t leave the country, then we would have to do it at home ourselves. So there was a lot of hesitation around that.

Nick: Now that Rita, you have had the procedure maybe several times, how was it for you?

Rita: It was very good, actually, because they made me very comfortable here in the office. For colonoscopy, I cannot say … Well, actually, I was very comfortable with colonoscopy, with the anesthesia, with the procedures here in the office. It was very comfortable for me.

Nick: That’s positive. You weren’t embarrassed or a bit scared?

Rita: No. I was not scared. I was not embarrassed because they made me laugh all the time, so I was not embarrassed in any way.

Nick: That’s wonderful to hear.

Rita: Yeah. They are great people here, Nicole, Jody, and the doctor, Dr. Connelly. They are so great.

Nick: Tamar, what about yourself? Obviously, being Rita’s daughter, you would have had concerns about the procedure.

Tamar: Did I have concerns about the procedure?

Nick: Yeah, did you have concerns? Any worries?

Tamar: Honestly, considering the fact that my mom has used drugs with such side effects that are still on the market that can even kill you, that can cause all sorts of damage to your organs, in light of the fact that she has had to use those drugs, I did not have any additional concerns about this procedure because we’ve tried everything else. So it was a risk worth taking.

Nick: I see. Nicole or Jody, is there something you would like to add?

Nicole: I would, actually, because Nathan always has initial conversations with patients to determine whether they are going to be appropriate people to have the treatment, and there’s a lot of things that go into that. And then we make sure that we have followup conferences with these patients, often through Skype, to make sure that we get to know them and they get to know us as well. I know that when Rita first made her decision to go ahead with the FMT program, and Dr. Connelly asked me to start the process rolling, it was a challenging process for me because we hadn’t had a patient like Rita in our clinic before. It seemed like it was going to be quite difficult for us with the hoist involved and managing everything that we had to manage from our end. But honestly, this has been really good for us.

Nicole: I’m a registered nurse, and Jody has done nursing in her past as well. I think that’s been really, really important for us in the practice because as I’m sure you can appreciate, the whole FMT process isn’t just about what a doctor can provide. It’s about what a clinic can provide. It’s important for us to make sure that we see each and every patient as someone’s family member and as someone who is potentially going to be embarrassed and upset about a procedure. Likewise, that’s to do with all of our patients that come to the clinic. But I think that we’ve made a lot of progress in this, and I think as a team we’ve done a really good job. And I think as a team, when I talk about team, that team is not just Nathan and Jody and myself. We have reception support, and our team includes Rita and Tamar as well. We’ve all had to work together, and it’s been a really great time. It’s unfortunate that they have to go back.

Nick: I see. So with the procedures, there’s also a level of service and care that you value, and as you just mentioned, you’re not just providing a service. You’re actually working with your patients, in this case, Rita and Tamar, to make sure they’re happy and comfortable and they sort of experience something positive and that will hopefully deliver the result they want.

Tamar: Yes, and they’ve actually shown a great deal of humanity in this. It’s not even just about doing a medical procedure. There was a lot of humanity involved in this. There was a lot of kindness and compassion involved in this with everybody here at this office. That is something that’s absolutely priceless and can’t be found just anywhere, so that’s very, very special. I will even give one example. We had a couple of problems with the hoist that had been rented here, and Nicole and Jody tried very hard to [inaudible 00:15:18] get them replaced and make sure we got the right equipment. Jody even used her own personal car and drove all the way to the city with me. We picked up the right hoist, brought it back, just so they could do the procedure in a timely manner. That is not something you would find in every single medical office. These folks have gone above and beyond in treating us with kindness and compassion and care, and that’s just something… Like I said, it’s absolutely priceless. There’s no amount of money that can compensate for that kind of humanity.

Nick: That’s certainly pleasing to hear. Going back to you, Tamar, you did a lot of research on FMT, and I’m sure there are people out there who are considering the procedure. Do you want to touch on the amount of research you did and why you believed in FMT as a possible solution?

Tamar: Sure. I did an extensive amount of research. Like I mentioned before, I stumbled upon actual scientific articles, some published in the United States, about the connection between gut bacteria and multiple sclerosis, which is the disease my mom has, so that’s what’s of interest to me as something that I would like to see a cure for that we haven’t yet seen a cure for and we were hoping that there would be. In that research, I’ve also discovered that this idea of using FMT on multiple sclerosis is being taken seriously now finally for the first time, also in the United States, in the sense that I know that the University of California in San Francisco has now started researching the impact of using FMT on people with relapsing-remitting types of multiple sclerosis. They are not doing that research yet on secondary progressive multiple sclerosis, which is the type my mom has, so that’s not available still in the United States. But it is hopeful to see and find out that it is being taken seriously, not just in one part of the world or a couple of parts of the world, but hopefully universally. So that’s what’s going on, and we’re hoping they will continue to do the research and work on people and that people will have access to treatment that they need and deserve.

Nicole: It will only be a matter of time before everything starts to get looked at seriously and they take FMT seriously, which by the way, has been going on since at least the 1980s in Australia, and a lot longer if you look back in other cultures. Unfortunately, in the meantime, there’s not many avenues that people can go to, and I think people doing things at home can and always will be a little challenging because if you’re not given the right information, there are a lot of ways that you can do things wrong. So I think it’s important that if you are going to look at doing things at home [inaudible 00:18:26] that you have the right training, which of course, we are also able to give because we’ve narrowed our program down to a fine art.

Nick: Okay, Nicole, a few questions about that. With FMT becoming more and more common, and I guess an increase in demand in Australia, do you see the procedure eventually being controlled to the point where it’s going to be more difficult for you to provide it, let’s say in the next couple of years?

Nicole: Yes. That started to happen last year. There’s been a lot of conversations about how FMT is being classified at the moment in Australia. It’s not currently classified as anything, and as Tamar mentioned before, Australia followed suit with the United States and clostridium difficile. The treatment of recurrent clostridium difficile is still gold standard to have the fecal microbiota transplant. Unfortunately, everything else [inaudible 00:19:32] is experimental. And the Therapeutic Goods Administration, which is basically Australia’s version of the FDA, are not sure whether to classify it as a drug or as an organ or as something different. I think this conversation was started in October 2018. Unfortunately, Nathan and I were unable to be at the conference, but we have spoken to numerous doctors that were at that conference. I guess it’s important for us to maintain a little bit of … independence I guess is the wrong word, but a little bit of our own flair on things, because when things start to get regulated too heavily, unfortunately, patients miss out.

Nick: Yes.

Nicole: I guess the flip side to that is that maybe there are some doctors that are not doing things the way that we do things. We screen very heavily. We are careful with the patients that we allow to have this done. But the bottom line for us is not about a financial gain. It’s not about a status to be held in society. It’s about the fact that we have a desperate patient in front of us, and it’s not the right thing to say no. This is for right or for wrong, how we run our practice.

Nick: You mentioned that obviously, somebody could be listening to this thinking maybe I want to try this treatment, and you’re offering, obviously, a solution. And as you just mentioned, you have a general concern and care for your patient above anything else. But there might be someone thinking, well, I’ll try this at home, which I find hard to imagine. But people actually do that, don’t they? They do try and self-medicate or self-treat.

Nicole: They do. Yeah.

Nick: What’s the problem with that?

Nicole: I guess the biggest problem is that they may not be choosing the right donors and that they may be putting themselves in harm, and that’s really important to get around that issue. We don’t just offer a one-off FMT program. In fact, we are very strong in this matter, and I won’t do it as a one-off because I think that it really needs to be run as a program. If we do have a patient that has a one-off FMT via colonoscopy, it’s very important to our practice that everything is managed over a 12-month period so that there are appointments in place and that patients know that they always have us to come back to at the end. That’s been something that we’ve learned along the way, and that’s what Jody has been really important with her part of everything and making sure that all of that happens and helping me create the best program that we can create, which is always a work in progress. We are always happy to talk about better ways to run the program, but we think at the moment that it’s run quite well and quite patient-focused because no two patients are the same.

Nick: Okay. So you’re basically saying you don’t have people come and do the procedure, then get them out the door. I believe you do several procedures, and then obviously, you’ll have aftercare. And you’re also wanting to improve your service and procedure.

Nicole: Yeah, absolutely. It’s all individual. It’s not like there’s just a way of doing it, and every patient gets the same thing. Everything is decided on a case-by-case basis with the doctor, which of course, we will speak about in a different podcast.

Nick: I see. I think we’ve covered quite a lot, and we are almost at I guess about 20 minutes, so maybe we should wrap up. But I would like to wish Rita and Tamar all the best, and I hope they also enjoyed their stay in Melbourne, Australia. Is there anything else that you would like to say, guys?

Rita: We are very happy. Actually, I am very happy that I came and I tried this FMT. It’s my first clinical trial. To me, I feel that I am in a trial because I don’t know what it’s going to do for me. But even if it does, I know that it’s going to take a long time, like months maybe, to work on me because I have secondary progressive MS and I have had this disease for 42 years, actually. I am very happy that I am here. I now know these amazing people, and I am very happy with my treatment.

Nick: That’s wonderful to hear.

Tamar: And Melbourne is a great city, so we’re happy to have visited on that end as well.

Rita: And now I am planning maybe to come every year.

Nick: I was just going to say I hope you guys come back again, but just for a holiday rather than for a treatment.

Tamar: That would be great.

Nick: Thank you so much for joining us.

Rita: Thank you.

Tamar: Thank you.

Nicole: Thank you.

Nick: 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.

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.