Do you have even more questions on Fecal Microbiota Transplant (FMT) that we didn’t cover in our recent podcast. In this episode, we bring you Dr. Nathan Connelly all the way from the Moonee Valley Specialist Centre in Australia to discuss more great information on FMT.
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Dr. Nathan Connelly…..Bio 1:20
Fecal Microbiota Transplant (FMT)…..2:37
The Conditions FMT Treats Most Successfully…..5:21
Repeat Courses of Antibiotic, Dismotility, and Prokinetics…..16:28
Weight Loss and FMT…..19:50
Less Common Conditions: Autism, MS, and Chronic Fatigue…..21:32
Donor Screening Process…..30:36
Cost of FMT…..35:51
Traveling to Obtain FMT…..42:47
Dr. Connelly’s Final Thoughts on FMT…..45:43
Most Important Thing People Can Do to Improve Their Health…..48:52
Dr. Connelly’s Least Healthy Fun Thing…..50:18
- A systematic review with meta-analysis showed FMT is safe but variably effective in IBD.
- Moonee Valley Specialist Centre
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FMT with Dr. Nathan Connelly
Dr. Michael Ruscio: Hey, everyone. Welcome to Dr. Ruscio Radio. This is Dr. Ruscio. And I am here today with Dr. Nathan Connelly, who is a pretty big FMT guy.
And the really exciting thing about having him on, in my mind anyway, is that he is not in the United States where they don’t have the same restrictions on using FMT. And I thought the conversation with him would be really interesting because of the ability to use FMT a little bit more broadly.
So, Nathan, thanks so much for being here. And welcome to the show!
Dr. Nathan Connelly: Oh, my pleasure. Thank you for inviting me.
Dr. Nathan Connelly Bio
DrMR: Can you tell people a little bit about what you’re doing, your training, some of that just kind of basic background stuff?
DrNC: Well, basically, I’ve been a gastroenterologist for approximately ten years. I trained on a liver transplant unit at the Austin Hospital in Melbourne. And I’ve been working in private for approximately about eight years—seven or eight years. I predominantly do work in private, but very much a community gastroenterology feel. It’s all the stuff you see out in the community rather than being highly specialized stuff, if you like.
DrMR: Gotcha. Gotcha. Okay, and you’ve been doing FMT since you first got into practice? Or is this something more recently that you’ve been doing?
DrNC: It’s probably more recent over the last two years. We started off with—I think as everyone does with their FMT. You start off with the necessary stuff, all the emergency stuff. So our first case was a little old lady who was dying of Clostridium difficile infection. And the results of that FMT were pretty spectacular. So that got my interest in seeing what else we might be able to use it for.
Fecal Microbiota Transplant (FMT)
DrMR: Gotcha. And we’ve already discussed what FMT is on a previous episode. But can you give people just kind of a really short summary on what FMT is?
DrNC: Well, FMT really goes down the whole dysbiosis line, which is to suggest that certain gastroenterological diseases and, by extension, diseases outside of the gastrointestinal tract—the reason why people have them is related to their bowel flora and abnormalities of their bowel flora.
And I like to think of the bowel flora being able to be manipulated in four different ways. One can use prebiotics, probiotics, antibiotics, and FMT. And they’re kind of your four tools that you have, if you like, for altering the bowel flora. And so FMT is kind of like the ultimate modifier of the bowel flora.
DrMR: I like that. I like that categorization system that you use.
DrNC: Well, it’s useful to conceptualize in your own head and then to look at how you can manipulate in those four ways and what evidence there is for manipulating in those four ways. It all centers around—I believe that gastroenterologists—we have our neurogastroenterologists who like to think everything’s due to the nerves in the gut. They hand out lots of pills and things.
But they tend to be fairly palliative in their approach. Or one can get to the root of the problem. The problem in gastroenterology and dysbiosis is measuring these. It’s very hard to measure the bowel flora in any meaningful way. And I think that’s where a lot of the suspicion around FMT comes from, is our lack of tools to properly measure the bowel flora.
DrMR: I would agree. But it’s also interesting to mention that even where we have good tools to measure, there still seems to be quite a bit of debate and controversy. So I had become more of the belief, the longer that I’ve been in clinical practice, that lab findings and object markers are important.
But in my mind, that’s as important as a patient’s response to a treatment. And so sometimes, the labs only can get us so far. And we end up in a position that would be more like FMT, I suppose, anyway, which would be treating more empirically and using the patient’s response kind of to guide if that is a successful treatment or not.
DrNC: Absolutely. And from a personal experience and where you want to go with this, if you’re completely free, then you can do that. The problem is that we’re not all free.
DrNC: And the people who like to do the studies or have the money to do the studies on this kind of thing like to have their tools and their objective measures and all the rest of it. That’s the problem.
DrMR: Sure. Sure. Yeah, and I can see both sides definitely.
The Conditions FMT Treats Most Successfully
DrMR: So you touched on this a little bit that you started with the more classical conditions like resistant Clostridium difficile infection. What would you say are some of the conditions that you see this most successful for? Obviously, C. diff. I’m assuming IBD also is pretty high up there. But what are a couple of the most successful conditions for this as treatment?
DrNC: In my experience, as long as you have a consent—it’s very, very hit and miss. But when it works, it works extremely well for diarrhea, predominantly irritable bowel syndrome if you’ve done your work excluding all the other causes.
So we’ve had a number of patients with refractory diarrhea who’ve had all their tests done and their biopsies and their breath tests. And they’ve been worked up. And sometimes, they’ve had attempts at palliation with drugs like Endep and Loperamide and etcetera. And they don’t work. Or they don’t want to take them. And we’ve had some spectacular success using FMT in those cases, generally one-shot FMT by colonoscopy. And we’ve had quite a few successes with that.
We’ve also had some success treating refractory constipation. I’d say probably the two biggest indications outside of the IBD group.
DrNC: The thing about the IBD group, in my mind, is there are trials that are very close. And there have always been some reported trials. As you would know, there is an effective FMT in colitis. But there seems to be fairly peculiar recipient and donor characteristics that we need to play out a little bit.
DrMR: Well, and that’s a question. I guess two questions come up there. The first, I guess, more just your own position on this. My thinking is since, as you said a moment ago, it seems to kind of be hit or miss, but when it hits it works well, but you have this hit-or-miss potential, this is why I like leaving the FMT more as a last—
DrMR: Last resort type of therapy. Would you agree with that?
DrNC: I do. And the other thing I often do in my practice with some of my patients—and this goes for the IBD group as well as the IBS group—is the antibiotic treatment. And we’ve got access to some very good antibiotics over here. I don’t know what’s FDA approved. I think your FDA’s a little bit more restrictive than the TGA over here.
But if I’ve got a really good response to antibiotic therapy, drugs like Rifaximin, Vancomycin, Doxycycline in combination, and they keep relapsing when you stop them, then that’s the patient you really want to go on FMT because they’re showing a dysbiosis kind of—they’re showing themselves to be dysbiotic kind of patient.
What you have to remember even with IBD is that all the patients are lumped together. They’re all supposed to have the same cause. The cause is unknown of course. We’ve got our suspicions. But they’re all lumped together.
My belief is that they don’t all belong together. There are different pathogenic mechanisms in different patients. And the whole IBD thing is just the end point of various different processes. That’s what I think. I’ve got no evidence for that of course. But I think it’s the reason why a certain subgroup of ulcerative colitis patients does not respond to biological therapy.
You’d think that biological therapy would work in everyone. Well, it doesn’t. That’s why FMT is there, I guess. So I do tend to stay very much still on the straight and narrow with the IBD patients. But I don’t believe anyone should have a colectomy without having FMT first.
DrMR: Oh, definitely. I certainly think we can support that. And you mentioned the subgroups of maybe ulcerative colitis or just IBD loosely that don’t respond to anti-inflammatory drugs or evenbiologics.
DrMR: And it makes me remember or think of something I’ve been tracking over the past several months, which is cytomegalovirus as a cause of steroid-resistant colitis.
DrMR: So that’s another factor that we may not really have an impact on the virome with antibiotics. And maybe this is an area where FMT through modulating everything really—we’re going to be transplanting viruses too really if we’re truly doing an FMT, or at least I would think. Maybe that’s another mechanism where there’s more going on than we really realize, which is why kind of a total re-colonization seems to work well.
DrNC: The whole viral thing is scary. If we have trouble measuring the bacteria in the gut, we’ve got no chance as it stands at the moment. I completely agree with you. We don’t understand what’s going on.
Some of my colleagues—some of my dysbiotic colleagues, as I call them—we think that this is all infective. It’s hard to believe it’s not. And since we lack the tools to be able to figure out what it is, that’s the problem. It could be viral. All of ulcerative colitis and Crohn’s disease could be a viral illness or unknown bacteria illness. It could be.
DrNC: And a lot of us think it is.
DrMR: And have you used anti-virals? Have you found any cases of CMV (cytomegalovirus) being a cause of any of these cases of IBD? And if so, have you used an anti-virals to any effect?
DrNC: Yeah. These patients generally who’ve got that degree of disease generally are in two or three referral hospitals over here. So my only experience really was back in the day when I was working at a tertiary referral hospital.
And my tertiary referral hospital didn’t have a particular interest in inflammatory bowel disease. Pretty much, I knew nothing about inflammatory bowel disease when I graduated from there. No, it was all, “Liver, liver, liver, liver, liver, liver.”
DrNC: So, no. This stuff’s all kind of either self taught, learned through going to conferences, or speaking to some local experts here who have an interest in the whole dysbiosis/FMT thing.
We’ve got a big trial—a couple of trials actually presenting very shortly that were done in Australia. One was done in Brisbane. One was done in Adelaide. And apparently, I hear the inside word that the trial is positive for the use of FMT in ulcerative colitis. But that’s all on the hearsay.
DrMR: Gotcha. Gotcha. Okay.
DrNC: They’ll be reporting in the first half of this year on their results. And I suspect they’ll back up another trial that was reported. I don’t know if you saw this trial. The one where they had had some success, but the success was all with the same donor. So they had one winning donor, and the rest were useless.
DrMR: I guess that donor might have part-time employment for awhile if they wanted it then.
DrNC: Well, we’ve got one of those donors. And our donor doesn’t use the toilet very often. She almost handed her toilet back, actually.
DrNC: For that purpose. So it seems like the demographic characteristic of a good donor is a young female, basically it seems. They seem to be the ones that hit more often.
DrMR: Really, that’s good to know.
DrNC: Yeah, even if we don’t understand.
DrMR: Well, I definitely want to pick your brain more on the donor piece in a minute.
DrMR: Couple of things that come up as you were making a few of those remarks. I know when Mark Davis came on we had talked about a systemic review—a recent systematic review.
Sorry. I have a bad habit of saying systemic, and one of our followers actually corrected me on that. So thank you if you’re listening. And bear with me as I try to get this meme out of my head here.
A systematic review with meta-analyses showed about a range from 20% to 60% effectiveness in FMT averaging about 45. I definitely think that the published literature substantiating FMT for IBD is growing, which is exciting and nice to see.
You also made a general remark that there is a lot that we don’t know. And I just want to take a moment to echo that for some patients out there who sometimes get so obsessive with these details and proposing these—some of the things that patients bring to me—I’m sure you see similar things—are so detail oriented and super theoretical.
And people are trying to string together seven to 10 different mechanisms to arrive where they are. And I’m happy people are doing health research. But I wish they could see inside my mind. And I think you probably are similar in this where the mechanisms and the conjecture and the speculation really don’t get you that far.
We have treatments. And we have treatments that we can use. And we want to try to line the right patient up with the right treatment. And a lot of times, it’s not this super-analytical mechanistic way in which we get there.
DrNC: Absolutely. I completely agree with you. I guess it’s the way that the patients conceptualize in their own mind what’s happening. But what I try to get my patients to understand is how—because again, what we discussed at the start, which is the ability to measure the flora, the ability to measure the products of the flora, the ability to measure bowel leakiness, if you like.
I hate that term, but I’ll throw it in there. Without the ability to measure, there’s almost kind of no point actually theorizing about it. This becomes very—it almost goes back to what medicine used to be. And that’s probably why some patients like it because, “Why does it work, Doctor?” Because it does.
DrMR: Yeah, it’s very empiric. Yeah.
DrNC: It is very empiric therapy. So is antibiotic therapy. So is prebiotic therapy and probiotic therapy. These things are all empiric. And I think we have to accept it’s empiric. And eventually when we have the tools to measure and we have the tools to look this up, then we’ll move away from the empiric.
But that’s not going to be for a long time. And no one’s that interested that they’re going to spend a lot of time or money doing it, in my opinion. There are some people making headway into this. You go to different conferences.
And there’s more and more stuff about the microbiome. But the stools are still very crude. And like you said, there’s a lot of debate about all of this. Until they tie some stuff down, it’s going to remain almost not worth going there.
DrMR: Right. And I just make that reminder just for the group of people that are really almost kind of getting so detail oriented and analytical with this, it almost kind of drives them crazy. And some patients come in.
And I can tell they’re really—they could almost have their PhD in microbiota research by the time they come to my office. And I just want to prevent people from going too deep down that hole because one of the things that we’ve talked a lot about on this show in the past is not tipping over that edge where you get so fanatical about your healthcare that you forget about friends, hobbies, life outside of your health.
Repeat Courses of Antibiotic, Dismotility, and Prokinetics
So, anyway, without beating that horse to death anymore, one other question I wanted to ask you, you mentioned patients that need repeat courses of antibiotics. And I’m sure you’ve probably heard the dismotility theory on SIBO.
And I’m wondering if you find with any patients, either IBS or maybe even IBD, that using a pro-kinetic agent helps prevent the relapse of their symptoms.
DrNC: Not so much in the IBD patients but certainly in the SIBO patients. The biggest group this comes down to is the bloating patient. The bloating patient is the patient where your heart kind of sinks because there are so many different mechanisms as to why people bloat and so many different theories out there.
And the different camps tend to be calling each other mad and all the rest of it. The whole thing is quite debatable. But if you believe in the whole SIBO small bowel constipation theory, then yes. The combination I like to use is Prucalopride, Rifaximin, and doxycycline for the very desperate patient who is very bloated. Seems to work quite well when the antibiotics alone don’t work well. So, yeah, I do believe in using pro-kinetics in that setting.
DrMR: And do you use them for a number of months and then taper off? Or what’s your kind of experience with that?
DrNC: Try and get the patient well. And then you try to withdraw. With SIBO, if you get a good clinical response, in my experience, if you withdraw too quickly, they get sick again very quickly.
DrMR: Gotcha. Okay.
DrNC: I don’t think you can just give them one week of doxycycline and that’s going to guarantee they’re better. I think you do need to—what I generally do is I hit them pretty hard pretty early, try to get a clinical response, and then try to taper rather than sort of building up because when you’re building up, you’re just throwing stuff around. You don’t even know if it’s working or not. So basically, get a clinical response, then taper.
DrMR: And you make a really good point again that this more kind of maybe old country medicine, if you will, or very medicine from antiquity that was very empiric-based and relied very heavily on the patient response to steer treatment, which I think there’s a lot of wisdom to that approach. And it also reminds me of—I’m not sure if you saw the study that they administered Rifaximin up to 12 weeks.
DrMR: Based upon the severity of the SIBO elevations dictated how long they gave a course of Rifaximin. So interesting that in this study, they noticed the higher the gas levels, the longer patients needed on Rifaximin.
And the other thing I took away from that study was the symptoms improved before the labs improved. They noticed that there was this kind of fact where the symptoms would start to improve, and then only a couple weeks later would that then manifest as a lab improvement, which again kind of reinforces the importance of monitoring a patient and listening to how they’re doing to help steer therapy.
DrNC: Absolutely. And I think also with these chronic gut symptoms, you need to do something for long enough. So I really don’t do antibiotic therapy for less than two to four weeks. I don’t believe any shorter duration is definitive if you’re going to get an improvement or not.
DrMR: Makes sense.
Weight Loss and FMT
DrMR: What about weight loss? Have you see any changes? I’m sure if someone has a very bad inflammatory disorder and they’re losing weight, then certainly an FMT, I think, would help them regain weight. But I think a lot of people are curious as to could there be a utility for treating overweight and obesity with FMT.
DrNC: Absolutely. And there are some pilot studies that are being done.
I think there was one in pre-diabetic obese men, looking at their markers, trying to use objective markers. And there were certainly improvements in their insulin sort of parameters, if you like, or parameters of insulin resistance with the use of FMT.
There are people out here who do FMT for weight loss, believe it or not, because there aren’t any hard and fast restrictions on the use of FMT. I don’t know whether they’ve published anything or whether they plan to publish anything.
But there’s enough data there to suggest it may work. I sort of haven’t really gotten into that myself. I kind of stick to the gut stuff. Well, I try to stick to the gut stuff. But it’s very difficult to stick to the gut stuff sometimes when we have one inquiry a week from the parent of an autistic child.
DrNC: Which is the big problem we’ve got here in terms of FMT and trying to stick to the straight and narrow.
DrMR: Yeah. I’m sure. It’s always tough when people are clearly in need of help. And you don’t want to withhold that. But you also have certain rules that you have to try to adhere to at least to some extent.
Less Common Conditions: Autism, MS, and Chronic Fatigue
And I guess with that, as a lead-in, with other conditions like autism or MS or there was another study on chronic fatigue, have you noticed? Have you seen anything? Do have any experience or any observations with any of these off-label uses, I guess we could say?
DrNC: I have extensive discussions with the person in Australia who’s done most of that work. And I would love his research to be replicated. I really would because the numbers look very good. But that research needs to be replicated elsewhere. And again, I think there definitely is going to be a role for FMT in extra-intestinal disease. I know they’re doing a trial of FMT for autism in Phoenix, I think, over there in Arizona. Arizona, yeah? Correct? Yeah?
DrMR: I’m not sure.
DrNC: Arizona Autism Research Group, I think it is, is doing a trial of FMT for autism.
DrMR: Oh, good.
DrNC: And I think it’s something like 70 or 80 trials ongoing of FMT in the United States last time I looked, which was a year ago. So there are probably twice as many now. So it’s about getting home and doing that research and doing it in a way in which it’s meaningful.
I think, again, this point you make, Michael, about not getting to wound up necessarily with mechanisms and objective stuff and all the rest of it—I think that’s very important for the trials because in many ways, it is an empirical therapy.
And in many ways, just the outcome is all that’s really important to start with because then the shackles will get loosened and we can start to use it because these therapies are really being sought by patients who are desperate and for whom the usual Western medical treatments have not helped. They’re not coming uncooked. They’re not walking up in their first week of having ulcerative colitis and saying, “I want FMT.”
DrNC: It’s been five years, six years, two years of all the drugs and no help and all the rest of it. So they’ve got to get on and do it.
DrMR: I agree. And I think a better method for the research—or maybe the most efficient method, I should say, would be to find what works. And then let’s discover the mechanism after we find what works.
DrMR: Because if we spend all the energy at mechanisms and then theorize from there, we may then do another study to eventually find it didn’t even work. So we wasted all that mechanism discovery for nothing.
DrNC: There’s stuff you can do, like you can taper down to stool. And you can freeze it and do it later. You don’t have to do it at the same time. You can store your stuff and then come back to it if the study is designed properly. But I think given the potential efficacy—and everyone knows it works. And everyone has got those stories of patients who are cured with the use of FMT. It will not go away.
Therefore, you really do need to get on and figure out the important questions that need to be answered. For example, protocol questions are very important as well. What protocol do you apply to each disease or each patient?
Or how do you modify your protocol according to how the patient is progressing? Because that’s one of the problems I have—different disease, different patient, different problem. What protocol do I give? Do they get a one off colonoscopic and ten and then weeklys? Or do you stop after the ten? That’s the big question.
DrMR: Right. Yeah, it’s a lot of just uncharted territory right now.
DrMR: And that’s maybe a good lead in to start getting to some of these more protocol-specific questions of best method of administration, frequency, donor compatibility. What are some of the things that you’re seeing there? Again, understanding this is very uncharted, but these would just be maybe trends you’re starting to observe.
DrNC: Again, it’s all disease dependent. For C. diff., for example, a one-shot bat at FMT will work usually. It doesn’t matter who your donor is. It doesn’t matter how much you give them. It just works.
DrNC: So you don’t have to be a genius to FMT someone with C. diff. The only thing you need to do is not to give them antibiotics afterwards.
DrNC: Which is what I see done or what I saw done the other day. And I have to re-FMT this person for their C. diff. associated with their ulcerative colitis.
DrMR: Oh, geez.
DrNC: Yeah, so they gave him antibiotics three days later, which is just ridiculous. So that’s the first point. For IBD, I still haven’t done enough to sort of deviate from a standard protocol of one-off colonoscopic followed by daily enemas over the next 12 days. So it’s initial five day, break for the weekend, then five days. And then weekly for at least a month and then decide where it’s heading. Are you winning, or are you not winning?
DrMR: Gotcha. What about the pill method? Have you found that to be an easier form for some people? Or have you tried it?
DrNC: Is it capsules don’t know. I just don’t in my mind understand. Capsules I would think would suffer from the same problems as probiotics. I don’t know if there’s enough data to suggest implantation persistence, all that stuff.
So I haven’t fiddled with it. I know that my mate Tom in Sydney is fiddling with it in a massive way and trying to get it right. But I don’t think he’s quite got it right yet. So it’s coming. And I hope it does come because it’ll make things a lot easier. But I don’t think they’re there yet. I’m not sure what the latest research is with C. diff. to where there’s any data with that. But that’s the point you’d start at, I think.
DrMR: Well, Mark Davis made a very interesting point where if you have something like very proximal Crohn’s disease or even something like SIBO, the capsules may have more utility there because you’re limited with what you can—through colonoscopic administration, you can’t really get into the same areas.
DrNC: Yeah. Yeah, absolutely. No experience, though, to be honest. I don’t have access to them. So again, that’s another area. Maybe it’s the reason why FMT doesn’t work so well for Crohn’s disease.
DrMR: Right. It’s certainly a plausible question and something hopefully we’ll get more answers to because it seems that we—looking at probiotics and some of the anti-inflammatory interventions that we have, it looks like ulcerative colitis tends to have better response than Crohn’s does. And so it’d be great to have something that would be more of a win for Crohn’s.
DrNC: Yeah. Conversations about FMT with patients contain the words “I don’t know” and “probably” or “maybe” a lot.
DrNC: It makes us ask, “Why am I sick?” “Don’t know.” “Why don’t I get better with FMT?” “I don’t know.” You just don’t know. These things we’re giving people, are they secreting stuff? Are they little drug factories? Or is it truly a probiotic kind of mechanism? Is it crowding something out? What is it doing? You don’t know. So I try not to worry about it too much. I said, “I don’t know because it’s going to work, isn’t it?”
DrMR: Yeah. Let’s get the patient healthy first like we’ve been talking about and then figure out exactly why afterward.
DrNC: Yeah. So therefore, it applies the same when you’re looking at other indications and other ways of doing it. Don’t know, don’t know, don’t know. Have to try it, see if it works.
And I think that’s one of the reasons why people get very nervous about FMT or my colleagues get very nervous about FMT because not understanding is very difficult for them. But they need to just sort of get over themselves a little bit and understand how safe it is, as well.
They’re saying it’s not talked about that often. It is incredibly safe. There aren’t a lot of—the bad case reports really centered around the use of top end FMT with nasojejunal tubes and all the rest of it. There were a few cases of severe aspiration pneumonia.
But from the other end, I don’t think there’s much in the way of adverse case reports. I think there’s one person who became overweight, but they probably just ate too much. So I think it’s incredibly safe therapy.
DrMR: Absolutely. In my examination of the literature, the side effects have been very minimal and very rarely reported. And that one case of weight gain, I guess Mark Davis actually knows the doctor that did that. And there was definitely some non-ideal methodology. And that only being one case report also.
So, yeah, I totally agree. It seems like it’s overall very safe. But that comes with the qualifier that you really need to be working with a clinician on this because there are important screening ideas that need to be done.
DrNC: Yes, absolutely.
Donor Screening Process
DrMR: And what are some of your screening processes that you run people through?
DrNC: So our process—the first thing I’ll tell your listeners out there is don’t use your dog. Okay. It’s not good.
DrNC: And don’t use an unscreened donor ever. And try to avoid using people in your own household. They tend to share the same sort of bowel flora that you’ve got. And your bowel flora is no good. Otherwise, you wouldn’t be talking about having one.
So, again, this patient whom I had the other day who got FMT for his C. diff. in association with his colitis, they used his wife and didn’t screen her. So it’s quite likely that she suffers from C. diff. as well, probably asymptomatic carriage, but you wouldn’t use her stool.
So what do we do? Basically, we start with the person. And we have a questionnaire of about 20 questions we ask. And we go through the patient’s general health, their travel, some of their lifestyle issues, and all the rest of it. So what you like—the perfect donor is a 20-something vegetarian female who doesn’t drink too much and poos like an elephant. That’s what you want. That’s your perfect FMT donor.
Beyond that, we then start to screen them up. And the most important test—apart from the blood-borne viruses, the HIV, hep B, hep C, HTLV—we test, pretty much, the blood for everything we can. And as far as the stool is concerned, we PCR up for all the parasites, bacteria, C. diff. obviously. But they’re the kind of test we do.
And it’s amazing how many people have blastocystis or Dientamoeba in small amounts. And they get screened out. I treat this—in the end, if you’re not rejecting about 90 to 95% of your donors, you’re not doing enough screening tests because that’s about what we get.
DrMR: Wow. That’s good to know. Okay.
DrNC: Yeah. We screen a lot of people. We tend to be fairly fussy, if you can be. If you can get enough people interested in being donors, you can be fussy. And we’re fussy.
DrMR: It’s interesting that the age piece is an important factor. But it comes back to something that I see in my mind as I really have been following the microbiota literature pretty closely for a few years now, which is the environment has such a large important on the microbiota.
And sometimes, you fall into what I think is an erroneous line of thinking, which is if we can just get the microbiota right, it’s going to fix every problem, which certainly I’m a very gut-centric sort of provider. I think there’s an incredible impact from the gut onto the body. But with some of the nuances of what some of the main phylotypes look like or what the microbiota stage will show, you definitely see the environment cues have a really big impact on this: sleep, jet lag, stress. And another one that seems to be important is age. And so it’s interesting that you find that a younger donor works better. And maybe that kind of reinforces the environmental impact on the microbiota.
DrNC: Yeah, this is all excluding C. diff. by the way. C. diff., use whatever you like. Just screen it up and give it because it doesn’t seem to matter that much for C. diff.
DrNC: So this is all excluding C. diff because it responds to anything. It probably would respond to dog poo. It probably would if you could do the trial. But anyway, don’t do that.
So, yes, on top of everything else, because we don’t know and because we can’t actually measure in any kind of credible way—because we can’t do that, you just have to go with what you think is the best in the end and what you can get.
DrNC: So screen everyone up. Get the best donor you can. And the other thing we’re trying to do wherever possible is trying to do two donors together to screen out of some of the donor effect. And this is where the next trial should go. I don’t think we should be doing trials with single donor. I don’t think we should. I think we should be doing trials with mixed donors.
DrMR: Well, it makes—I’m definitely making a jump with this analogy. But if we look at a lot of the probiotic trials, many—I would say most—of the probiotic trials show that using a multi-strain species works better than using a single strain species.
DrMR: So it kind of borrows along that same concept to where if we can present a higher diversity of bacteria into the ecosystem, we have a better chance of having good results. Especially if the donor has something that may not be ideal, maybe even slightly pathogenic, perhaps the other donor’s microbiota could—
DrMR: Out-compete or inhibit that as a kind of hedge.
DrNC: Yeah. It’s trying to remove the donor effect.
DrNC: Because the donor effect is huge. It is. From the trials that I’ve seen, it’s looking like a big effect. And when you get a trial when no one’s stool works except for one donor, and eight out of the nine go into remission, that’s a massive donor effect. You can’t give them that.
DrMR: Yeah. Yeah. Well said.
DrNC: I think that was the last trial I looked at. So it’s trying to remove that donor effect as much as we can.
DrMR: Yeah, I totally agree.
Cost of FMT
Regarding cost, and it’s another issue for patients. Now, there are probably people listening to this from all over the world. And there may be insurance coverage if they live in a certain place or cash pay if they’re in another. So what’s some broad information regarding what kind of cost commitment someone may be getting into with this?
DrNC: It kind of depends on how they want to do it and how much they need. To get good donors who do the right thing and all the rest, we pay our donors. We do because that pays them for their time and the inconvenience and all the rest of it.
DrNC: And also, the cost of mixing it all up and all the consumables and all the rest of it. The patients, we do offer a home FMT program, so the patients—we teach them how to do it. And they can do it themselves at home. This is for the post-colonoscopic interval one if they’re just going to go with enemas only.
DrNC: The patient actually can do it themselves. If they’ve got a screened donor who’s appropriate and know how to do it, you can do FMT yourself at home. And that reduces the cost markedly. So what we often do is we’ll get patients in.
We’ll do the first three or four in the rooms. And then we’ll get them to do it themselves at home either with mixing up their own FMT or using it from the rooms. And that way it does reduce the cost significantly. But the cost of having FMT in Australia does run into the low thousands as a broad guide.
DrMR: Gotcha. Gotcha. I like your idea of trying to do a hybrid approach to bring down the cost. That’s smart.
DrNC: Yeah. And the other thing is, technically—Australia’s a big country, and we get patients from other states who want to do it. And they don’t want to stay around in Melbourne for two months, having their FMT.
So what we try to do is before they even have it is to organize an out for when they’re at home. So organize a local donor who’s screened up, seems to be appropriate, and continue on with it at home, doing it themselves if they can. If you’ve got a motivated patient, they’ll do it. And it’s not that difficult.
DrNC: Technically, it’s a very, very easy thing to do.
DrMR: Well, I certainly think that if someone has gotten to a point where their diet is just incredibly restrictive and they have to be on a very elaborate treatment program with a mixture of herbal and pharmaceutical drugs, that this may be something that could get them off a lot of that and on a less restrictive diet. And it certainly seems to be kind of cost and energy effective.
DrNC: Yeah, that comes back—again, that depends on the problem. But if the question is where does it fit in the individual? And I think where does it fit with a certain individual depends on the individual and where they’re up to and how well educated they are.
So when I’m doing my consent process, it’s kind of like—the initial interview’s like maybe an hour, just to talk to the patient about where their head’s at and why they want to do it. But I’ve made a decision. If you’ve got a consenting adult who knows what they’re in for and have done their research, I’ll FMT anything because in the end it’s the patient who decides what they want.
They need to be educated, though. They need to understand what they’re getting into. And they need to understand the process behind it. But beyond that, I don’t look too much at the disease, to be honest.
DrNC: If you’ve got chronic fatigue and you want me to FMT you, I’ll do it as long as you understand.
DrMR: Yeah, as long you—yeah. And I think of course to give consent, one has to be aware of all the information regarding a treatment.
DrMR: So it definitely makes sense.
DrNC: Which is easy for a condition like chronic fatigue because there is no treatment.
DrNC: For ulcerative colitis, it’s different. Ulcerative colitis is the one I struggle the most with at the moment because having been trained in sort of the classical way of managing these conditions, I do tend to stick to managing it that way.
And I’m sort of saying to patients the trials are trials are trials are trials. The big hope, I always think, with FMT and ulcerative colitis is your new patient who’s going to be difficult. They’ve got bad prognostic signs. They’re going to probably end up on biological therapy.
One ought to FMT them straight up because this patient may be better in the end with that approach rather than going down the biological line. They might get better quicker. They might have a better quality of life.
And the actually cost to the health system might be significantly less if you do it that way. That’s the great hope I’ve got for ulcerative colitis, not necessarily your patient who’s completely cooked, who’s burnt out, who’s gone through all the drugs and the colectomy. But that’s the patient who classically FMT is applied to in a rescue way.
DrNC: But the real hope I think is seeing UC patient who hasn’t had the disease that long but has got bad prognosis disease and might want to circumvent going down that route because it certainly—again, more of the data with UC suggests the earlier you do it, the more successful it is.
DrMR: That makes sense. Okay.
DrNC: But it’s hard to get them over the line to do that. And that’s where it comes into the design of future trials regarding FMT.
DrNC: It’s very situation specific. So even if this trial they’re doing in Australia doesn’t pan out, there’ll still be other trials that need to be done to work out where it does fit in the treatment course for patients with ulcerative colitis, for example.
DrMR: Right. And I totally see what your hope is kind of centered at or looking to achieve which would be to save someone. It may be a year of a really tough road for someone to figure out that this drug didn’t work. That drug combination didn’t work. This diet didn’t work. Sometimes, that’s a process someone has to go through.
DrMR: Because there’s a pro and con there. You may discover a very simple, safe treatment works really well.
DrNC: Yeah, sure.
DrMR: But I think the prognostic indicators, like you said, which as I understand them, there are a few which would be elevation of the antibodies, potentially histological findings—
DrMR: And then also the duration and the frequency and the severity of relapse. Or the more quickly someone relapses, the longer the relapse tends to be, and the shorter the window in between the relapses all tend to be prognostic indicators for how severe a case is going to be.
DrMR: Would you add anything to that?
DrNC: Yeah. I think you can tell the patient’s going to end up on vedolizumab or infliximab. You can pick them pretty early with ulcerative colitis. They turn up sick, and they stay sick. You can’t get them below 25 mg of Prednisolone while you’re working through all your other options. In Australia, you can’t give biological therapy until they’ve had at least a Thiopurine and probably Methotrexate, as well.
Traveling to Obtain FMT
So you’re looking at—giving it three months each, you’re looking at six, nine, 12 months to even get someone on biological therapy if you follow the rules exactly, which I know some of my colleagues don’t. But we’ve got certain rules with the use of biologics.
So you’re right. You’re committing them to 12 months of fluctuating corticosteroids. Not everyone can pay to have poorly absorbed budesonide, which is not covered by our health system over here. So some patients don’t want to do that.
DrMR: Right. One other thing I wanted to ask you about which I’m sure—if there’s someone listening to this, this may be a question that was running through their mind. Let’s say they live in the United States.
DrMR: And they’re at a point where FMT may make sense for whatever their condition is, would they be able to screen a couple donors that are local to them remotely with your clinic and then maybe go to you for a few procedures and then fly back to the States and do things at home from there. Is that kind of remote model possible for people?
DrNC: Absolutely possible. If they want to Skype me, they can Skype me from the U.S. We can talk about it. And yes, that is possible. I don’t want to flag any U.S. laws because I do like the country and want to come visit again.
So I hope not flagging any local regulations or anything, which I don’t think I am, yeah, absolutely. And I think—again with the whole colectomy story, I can understand where the FDA is coming from with this. I can. But I also think if you’re looking at a patient with UC who’s looking at a stark choice of colectomy versus an FMT, is it ethical to withhold the treatment? Is it ethical?
DrMR: Good question.
DrNC: I think it really does skirt on the boundaries of ethics to withhold that therapy when you know there is a group of patients who respond just because you can’t work out who responds and who doesn’t and why they respond and why they don’t and just because it’s all not known about to the nth degree, which you probably never will know that to the nth degree, I don’t think it’s ethical to withhold that treatment because we know that colectomy is not the panacea. It’s a cure of sorts.
But you’re looking at four to eight bowel actions a day, a higher sense of sexual dysfunction, permanent loss of quality of life. There are consequences to having colectomy. It’s not just, “Oh, I’ll have my bowel out, and then I’ll be fine.” It doesn’t work like that.
DrMR: Sure. Yeah, totally.
DrNC: And there’s pouchitis. I don’t think anyone’s really thinking about that. Some of the other indications, sure, be restrictive or prescriptive regarding it. But I think for the colitis group, I think the FDA is skirting a little bit on the edge of interfering with a very ancient kind of relationship between doctor and patient. And I think the ethics of it are interesting.
DrMR: Yeah. I think you make some great points there.
Dr. Connelly’s Final Thoughts on FMT
Anything else you wanted to mention. I have a couple closing questions for you.
DrMR: But anything else you wanted to mention as we kind of bring things to a close?
DrNC: No, not really because I’m very happy to speak to anyone from the U.S. about this. I have got patients from overseas. It’s difficult. And it’s more of a guidance kind of thing in terms of helping people work their way through it. I think home FMT is doable. It is.
You’ve just got to have the people screened up. And there’s a huge amount of stuff on the internet about how to do your own FMT. I think, as doctors, we need to get involved in that little process so that we can help people do it safely.
DrMR: Sure. Makes a lot of sense.
DrNC: Yeah, I don’t think this should be completely controlled by the medical profession. I don’t. I think this belongs to everyone.
DrMR: Well, Mark Davis made some great points. There’s a foundation in the States that’s essentially all about empowering and educating people to be able to do this on their own. And so that kind of rings true to what you’re saying to allow this to not be such a regulated treatment, that there can be more access to all—responsibly and with good education, but more easy access to it.
DrNC: Yeah. In Australia, we have people doing colonic lavage. It’s not even regulated as far as I know. But it’s a whole lot riskier than having FMT.
DrMR: Yeah. Yeah, there’s a big difference from where I am to where you are with regulations. Absolutely.
DrNC: Yeah, washing high-powered water up your backside, there’s a reasonable incidence of perforation. FMT, there’s no—this doesn’t exist. Now, there needs to be some guidance. But I think the danger is if we try to regulate too hard on this, people are going to do it anyway. And they’re not going to do it in a safe way.
DrNC: So I think we do need to get involved in that conversation.
DrMR: Yeah. That’s an excellent point.
DrMR: Excellent point. And what is your website? Or where can people track you down or hear more from you if they wanted to?
DrNC: Okay, so our website is—that’s a very good question. Where is our website? I’ll have to look it up. Here it is. Sorry. It is—oh, hang on.
DrMR: If you’re not sure, we can put in the show. We’ll put it in the show notes with the transcripts for this call no matter what.
DrNC: Yeah. It’s—I can’t believe I don’t know my own website. I never look it up. Just hang on a sec.
DrMR: That’s all right.
DrNC: Give me two seconds, and I’ll—
DrMR: Sure. I really put you on the spot with that one.
DrNC: So the website’s actually MVSCentre.com.au.
DrNC: That’s our website.
DrMR: All right.
DrNC: And there’s stuff on there about me and the Centre and all the rest of it. I run a practice. My wife runs a practice with me. She’s very into the whole FMT thing, as well. She’s a nurse and the practice manager. And we work together on this. So there’s two of us here doing that.
DrMR: Gotcha. Great. All right. So one or two questions to close then.
Most Important Thing People Can Do to Improve Their Health
DrMR: What would you say would be the one most important thing for someone to do to improve their health after diet and lifestyle? We’ve harped a lot about that. But after diet and lifestyle, do you have one thing—if you could only do one thing with a patient or one thing with someone, what would that one thing be?
DrNC: So beyond—are you talking about drug? Or are you talking about a—?
DrMR: Anything. If your hands were tied and you only could do one thing for a patient to help improve their health, what would it be? And it’s whatever you want to go with here—something that’s really effective that you think is a very important part of the healthcare picture.
DrNC: If you don’t count—I think healthy sleeping habits are very important. But you might count that under lifestyle. I think anything that gives the patient better mental well-being, I think that’s the most important thing in this world to quality of life is what makes the person happy, if you like, and what gives them mental well-being.
So in terms of what one thing would do that, I’m not sure. But certainly good sleeping habits are very important. But beyond that, I don’t know. I really would have to go away and think about that question.
DrMR: That’s all right. I know it’s a tough one. So it’s okay.
DrNC: It is a tough one, yeah. Tough one. Yeah.
DrMR: Yeah, right?
Dr. Connelly’s Least Healthy Fun Thing
One other one that may be a little bit of a curve ball but curious to get your take on this. And quickly I’ll give the preface. We talk a lot about health on this show. I think a lot of our audience is very into health.
Sometimes, if you are too into health, you forget about other non-health-related stuff that’s really fun like maybe staying out too late and having a drink with a friend or getting some off-plan food at a really good restaurant. So with that as a preface, what is maybe the least healthy but most fun thing that you’ve done lately?
DrNC: Yeah, the poisons in one’s life that we all do. I think that is very important. And the most fun thing I did recently was going out for a large Chinese dinner with my family and just eating whatever we wanted. And we are fairly health conscious. And we all exercise and all the rest of it.
But just going out and having a nice meal and not worrying about what you’re eating, I think the point you make about not over fixating is very important. One does need to enjoy life. And you need to have your treats, which is something I do remind my patients of as well. That’s probably the last really fun thing I did. I had cigar also at one point in the last month. That was nice.
DrMR: Those both sound pretty good to me.
DrMR: All right, sir. Well, thank you so much for your time and having the conversation with us. I think people will get a lot out of this. And I love the work that you’re doing. And if you have anything new or exciting come up and you want to talk about it, feel free to shoot me an email. And we’d love to have you back on anytime.
DrNC: Oh, that’d be fantastic. If your FDA does start relaxing their stuff, I’ll be keeping an eye out on them. So hopefully, there’s some good data around the corner that we can move forward with this.
DrMR: Absolutely. I totally agree.
DrNC: Okay. Good on ya, Michael.
DrMR: All right. Thanks again. Take care.
DrNC: Okay, bye.