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Northwestern Medicine's Fecal Microbiota Transplant Program

Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me, we have a panel today with Dr. Aaron Cohn, he's a gastroenterologist with Northwestern Medicine in the north region; and Dr. Eugene Yen, he's an Associate Professor of Medicine in Gastroenterology and hepatology at Northwestern. And they are here to highlight the new Fecal Microbiota Transplant Program at Northwestern Medicine.

Doctors, thank you so much for joining us today. This is a very exciting topic and an exciting program. Dr. Yen, I'd like to start with you. Can you tell us a little bit about your areas of clinical and research focus as you're new to Northwestern Medicine? Tell us a little bit about yourself and from whence you came.

Dr. Eugene Yen: Thanks. I'm really happy to be here. I've been a gastroenterologist for the past 15 years. And prior to joining Northwestern, I worked in a research group in the northern suburbs. And my research was in inflammatory bowel conditions, Crohn's disease, ulcerative colitis, and microscopic colitis. But in around 2010 was when I performed one of the first fecal microbiota transplantations for folks who had recurrent C. diff infection and, over the years, built some expertise in that and, at one point in time, was running one of the largest programs for FMT for C. diff infection. So, my arrival in Northwestern was timely and I'm happy to continue that research here.

Melanie: Well, we are certain glad that you have joined Northwestern Medicine. And Dr. Cohn, I'd like you to set the table for us about C. diff, the prevalence, what you've been seeing in the trends, and kind of give us an indication of the scope of the problem that we're discussing here today.

Dr. Aaron Cohn: Thank you so much for having me. I'm excited to be here to talk about this epidemic, and it truly is an epidemic. US hospital discharges with C. diff infection actually doubled between 2000 and 2008, and there's been an increase in the annual C. diff infection incidence of 43% from the years 2001 to 2012. Cases of recurrent C. diff infection, which is defined as multiple greater than two or equal to two C. diff infections, have increased 188% over that same period, 2001 to 2012. CDI is what I call C. diff infection, is by far the most common healthcare-associated infection in the United States with 500,000 cases and 30,000 deaths in the US every year.

Melanie: Wow. It certainly is an epidemic. And Dr. Yen, I'd like you to speak about advancements that have been made in the management of C. diff and clinicians that are seeing recurrent C. diff. We're here today to discuss fecal microbiota transplant. I'd like you to tell us a little bit about that and the evolution of this type of treatment and really the rationale behind it.

Dr. Eugene Yen: Yeah, sure. I'd like to just add from what Dr. Cohen had said, was that, you know, we often think about C. diff in the pre-2000 and the post-2000 terms. So, a lot of the statistics that he gave you were of the post-2000s. And I think, as a clinician, I recall those times in that it was relatively easy to treat C. diff infection back then. And then, post-2000, you're hearing what we're experiencing, which is it's harder to treat, people tend to recur more and people tend to have a worse outcome nowadays. And then, the other thing that's really been evolving is more of these community-related events as well. So, I think we used to associate this as just purely a healthcare-associated problem. Whereas now, we're seeing this much more commonly in the community setting.

I think Aaron also mentioned about our therapies and how people are recurring more. And I think that nowadays, when a patient has their first bout of C. diff, we tell them that they have a 30% to 50% chance of recurring, getting this C. diff again. And I think that that's not something we told people 20 years ago. And so, I think how this field has really evolved was that we went from giving one antibiotic for C. diff to giving different antibiotic for C. diff to now giving a third or a different antibiotic for C. diff and we're trying different antibiotics to treat our C. diff. Unfortunately, I think we also recognize C. diff as a problem that's sometimes caused by antibiotics. And so, I think that that's what generated a lot of the other discussions as to other therapies for C. diff, including FMT or fecal microbiota transplantation.

And so, I think this FMT's been given for quite some time prior to my doing this. I think it was originally described, you know, in 6th Century China. The veterinarians have been doing this in veterinary medicine for different reasons as well. And I think that, as a clinical practice, FMT has been given for C. diff as early as reportedly in the '80s. And so, I think certainly, FMT did not really make its way to sort of more of the mainstream until some of the recent studies were published after 2010. And so, for the past decade, this has been something that was initially met with some cynicism but, at the same time, with all the data and the head-to-head studies that were done, has been more accepted as a main practice. And if you look at our guidelines now for treating C. diff for people who have multiple recurrent C. diff, FMT is now part of that practice recommendation.

Melanie: Well then, Dr. Yen, I'd like you to expand on clinical practice guidelines and indications for the procedure. Can you please speak about patient selection? Who is a candidate for this? And tell us about those guidelines.

Dr. Eugene Yen: Because our antibiotics are effective for treating C. diff, I think currently our guidelines recommend the use of either vancomycin or fidaxomicin are two separate antibiotics as treatments for C. diff infection. And then, I think that when you have multiple recurrences, the first recommendation is to take a longer course of those antibiotics and ,then if you have another recurrence, fecal microbiota transplant. I think that's based on the current evidence that we have right now. And I think that, with time when the data becomes even more robust, those things might change.

Dr. Aaron Cohn: There's already people tinkering with this, who are thinking about using FMT as the first treatment for induction. So, there's people already ahead of the curve, so to speak. But the majority of patients do get better after the first round of appropriate antibiotics, which to be clear is vancomycin. It used to be metronidazole, but Vancomycin is now the recommended first-line agent. But like Dr. Yen said, we always warn patients that up to 30 to 40%, even 50% of patients can get a recurrence, unfortunately. And I think that just speaks to how fragile our ecosystem is. And by ecosystem, I mean the microbial diversity that we have inside of our gut. And when that gets altered, we feel the effects of that.

Melanie: Well then, Dr. Cohn, speak about the procedure itself. How is FMT administered? Tell us a little bit about that.

Dr. Aaron Cohn: Thanks so much. So, there's different ways to administer a fecal transplant. Of course, first, you have to get the supply, which is stool from a healthy donor. And the stool is, of course, composed of a healthy, diverse, rich environment of microbes. And you could administer this through a colonoscopy. A colonoscopy is, of course, a scope that you insert into the colon through the rectum. You advance it all the way to the proximal end of the large intestine or into the distal end of the small intestine. And you transfuse or infuse the stool material. So, that's through colonoscopy. And from a patient's perspective, the process of preparing for a colonoscopy is exactly the same as what you would do for an average risk screening individual.

Then, there's also the ability to infuse the stool material just through an enema, where you don't have to do the whole prep for a colonoscopy, but you just get the slurry infused through the rectum, per rectum. There's also the ability to do it by upper endoscopy where the patients get sedated and you do a standard upper endoscopy. You advance the scope as far as you can past the stomach into the small intestine, and you infuse it through there. Sometimes you would give a promotility agent to help the stool get to the large intestine as quickly as possible.

And lastly, we're developing oral capsules that have fecal material inside the capsules. And they're designed to dissolve later when they get into the large intestine or distal small intestine rather.

Melanie: That is absolutely fascinating. And Dr. Yen, what are the parameters for success? How are you measuring a successful transplant? And are the patients then still colonized by C. diff after the transplant and without active infection? How do we know?

Dr. Eugene Yen: Yeah. You know, I, think that the good news for most people who have C. diff infection is that their symptoms are pretty predictable. And while everyone's a little bit different, an individual patient usually has the same experience. In other words, when they get C. diff, they know exactly what that is and they know what the symptoms are. And so, that's essentially the followup. I think that most of my patients are able to tell me very eloquently what their C. diff is like and how fast they get C. diff after they stop their antibiotic therapies. And so, essentially, we know that that's going to happen again sometimes in select individuals. And if we're successful with that, that's not going to happen. And so, that's the extent of the followup.

You mentioned about testing before. Often, we recommend not testing for cure to see if it's gone because many people are colonized with C. diff. In many hospitals, they won't even test to see a sample because we already know that about 10% of the population is a colonizer or they carry C. diff and they're not having any problems. So, it's not just having C. diff is what's going to cause you a problem, it's having C. diff and having the right environment for C. diff to cause illness. And so, the fact that you have C. diff inside of you doesn't necessarily mean that that's going to be a bad thing. But certainly, having the symptoms of bad C. diff infection are more important.

Dr. Aaron Cohn: Yeah, I think that really plays into the nature of our human body interacting with our bacterial population inside our gut. So, it's okay to have C. diff as one of the microbes colonized in your gut. But if it overruns the rest of the bacteria and acts like an invasive species, all of a sudden the ecological environment is perturbed and you get toxin released from the C. diff bacteria. And then, the colon can no longer function the way it should, and it becomes inflamed and patients experience the diarrhea. So, rather than testing for C. diff, it's much more important to follow their symptoms.

Dr. Eugene Yen: I'll also add, I think people are often talking about like what it takes to have a healthy microbiome. And I think just to keep in mind, a healthy microbiome also includes bad things as well. And I think that when you look at even the healthiest individuals, they have some really bad bacteria inside of them, but they all live in harmony. And I think that's how we would define that. So, it's not just the good stuff, it's also the bad.

Melanie: Well, doctors, as this program is new, can you tell me about your outcomes or how patients are tolerating this procedure? Dr. Yen, why don't you tell us?

Dr. Eugene Yen: Well, in my experience, I've been doing this for over a decade. And my experience as well as everybody else who does this is that we have a select group of individuals that have recurrent C. diff infection that we estimate their recurrence rate without FMT is greater than 70%. And so, that's where we're starting at a base. And for those that get an FMT, our success rates are over 90%. And in our institution, it was 92% and that sort of seems to be the standard number in terms of the amount of success. So, over time, we've helped a lot of people with this condition with really great success rates, and that's our expectation.

Melanie: I'd like to give you each a chance for a final thought because this is a new program, such an exciting time in your field. Dr. Cohn, gut microbial replacement therapies have been discussed for a host of other conditions. What other conditions do you see this being successful in your practice? Do you see FMT being used for other IBD conditions in the future?

Dr. Aaron Cohn: Yeah, it's a great question. By far and away, FMT to me is most exciting for C. diff because the results speak for themselves. It's safe, it's well tolerated, it's literally like magic. There's not many things that we can do with this safety profile and this efficacy. And it's such a relief when you find patients who are so desperate, who have been treated again and again and again with antibiotics and had their life thrown into pieces and to come and get a simple procedure that cures them. That is the reason most of us became doctors for patients like that and stories like that.

And when we saw such great success with C. diff, we immediately started thinking about could this be used for other conditions? And there's been a huge, huge, robust increase in studies that have looked at the differences in the microbiome between a healthy population, some kind of control group, and pick your disease from epilepsy to cirrhosis to Parkinson's disease to dementia and obesity, you name it. And they always seem to find some type of difference.

The tricky part is we don't know if it's the chicken or the egg. And when we try to give FMT treatments, we're not really seeing the same type of response that you would expect if these diseases are solely being driven by a shift in the microbiome. When I was a fellow, we were doing fecal transplants for C. diff, but we were also studying it for the use of ulcerative colitis, one of the types of inflammatory bowel disease. And we had so much excitement about this use and we were thrilled that we saw some people get better, but it wasn't statistically significant. And that's been, unfortunately, the pattern for most of the studies that I've looked at. It's hard to find a robust improvement, which makes me think that the microbiome has a role to play. But patient selection, donor selection, further understanding the pathogenesis of IBD, further research is going to be really important to figure out how we use this for other diseases like IBD in the future.

Melanie: And Dr. Yen, last word to you. What would you like to tell referring physicians, other gastroenterologists that are seeing recurrence of C. diff, whether community-acquired or healthcare setting about this new program for FMT at Northwestern Medicine and when they can refer their patients for a consultation?

Dr. Eugene Yen: Yeah. Thank you. So, I really enjoyed this talk and I think we're currently in a place now where we can accept all referrals for recurrent C. diff infection. I think that the folks that respond best to FMT are those who have had multiple recurrences of C. diff that respond nicely to antibiotics, but recur shortly after stopping antibiotics. And so, I think if there's any question of that, certainly our team is ready and equipped to see patients who have recurrent C. diff infection and to see if FMT is the right thing for them to do.

Melanie: It's such an exciting program. Thank you both for joining us and sharing your incredible expertise on this topic, because it is not something that is commonly known for other providers. So, this is an excellent program and we'd like you to come back on, join us anytime and update us as the program continues to be on the rise.

And to refer your patients or for more information, please visit our website at breakthroughsforphysicians.nm.org/gastroenterology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine Podcast for physicians. Please always remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.