Gut Check: Maria Vazquez-Roque, MD on Fecal Microbiota Transplantation
In this Gut Check podcast, Dr Brian Lacy hosts Maria Vazquez-Roque, MD, to discuss how fecal microbiota transplantation can be administered in the treatment of C difficile infection and potentially other colonic diseases.
Brian Lacy, MD, is a professor of medicine at Mayo Clinic-Florida in Jacksonville, Florida. Maria Vazquez-Roque, MD, is an associate professor of medicine in the department of Medicine at the Mayo Clinic in Jacksonville, Florida.
TRANSCRIPT:
Welcome to Gut Check, a podcast from the Gastroenterology Learning Network. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and I am absolutely delighted to be speaking today with Dr. Maria Vazquez Roque, associate professor of medicine in the department of Medicine at the Mayo Clinic in Jacksonville, Florida. Dr. Vazquez Roque is an expert in motility disorders and brain-gut disorders of the gastrointestinal tract. However, another area of expertise which we'll discuss today is that of C difficile colitis, and today we're going to focus on fecal microbiota transplantation, which we'll refer to as FMTA procedure oftentimes used to treat recurrent Cdifficile colitis.
So Dr. Vazquez, welcome, what an honor to have you on our podcast today. Although the topic of FMT or fecal microbiota transplantation may be new to some of our listeners, it's not really a new treatment. The first recorded use was approximately 1800 years ago in China, in approximately 300 AD, where a Chinese physician first treated severe diarrhea and food poisoning with a stool transplant, which he called yellow soup—not very appetizing. Then in World War II, a German neurologist reported that Bedouin tribes treated soldiers suffering from dysentery with stool from camels. But it really wasn't until approximately 1958 that stool transplants for c difficile colitis first took place in the United States. This timeframe, at least to me, is fascinating. Why did it take so long for FMT to become accepted by the medical community?
Dr Vazquez Roque:
Well Brian, thank you so much for the invitation and really excited to be here with you and talking about this topic that's so near and dear to me. I'm fascinated by the history and because I have that usually in my talks, I do like to talk about the history so we remember where it all started. And you're right, I mean there is a significant gap in when it initially was being done with these Chinese physicians and then later in Germany. But it's interesting, I think ultimately there was a great deal of an issue of acceptance from the medical community and even more so from more, and you talk about 1958, and that was actually for even patients that were having severe pseudo colitis and they usually, they did it really with potential surgical patients. And that's kind of where it started to pick up again, if you will, in the modern era of medicine.
And then subsequently an infectious disease specialist in Minnesota, actually in Duluth, Minnesota. Dr. Bachan really took it up again and really started to publish the more earlier papers, if you will, of the role of fecal transplant from a standard stool donor or a known stool donor in patients that had recurrent c difficile infection. But I think too, part of the acceptance was that it might've not been a recognized problem for many years, but as medical issues started to arise, more complex patients coming into the hospital systems c diff became a challenge. And even to this date is the number one hospital acquired infection. So I think obviously the awareness that throughout the medical community has become much, much greater obviously and accepted these, this is a treatment option for patients and patients themselves. Right now, majority do not have any qualms because they've been through various episodes of c difficile infection.
Dr Lacy:
That's really an important fact for our listeners—the number 1 hospital acquired infection. And so I know you perform this treatment at Mayo Clinic for patients with recurrent C difficile colitis, and you kind of have already spoke a little bit about the acceptance of this, but patients frequently ask where does this sample come from? Where did it come from, and are there quality controls associated with obtaining this sample?
Dr Vazquez Roque:
Yeah, so when we talk about fecal transplant, obviously that has changed tremendously in 2025, but specifically when we speak about what's a standard donor fecal transplant, essentially it is looking for a healthy donor the same way that for a solid organ transplant, for example, let's say a lung transplant, you get a healthy lung and transplant that into a patient with a disease lung. And this setting is slightly different because patients don't receive immune suppression after a stool transplant. It's mostly a stool therapy, for lack of better words, but we get a healthy donor. Our donors have to go through extensive assessment making sure their medical history, no high risk behaviors that could be putting at risk for any communicable diseases. But then the donor has to go through extensive stool testing and blood work from a testing perspective for communicable diseases—for example, HIV, syphilis, hepatitis—and there may be some regional infections that may be more endemic in certain areas of the US that the patients may get additional testing. So it's a pretty robust testing profile that the donor goes through on a regular basis similar to when we for blood donation, they're very strict guidelines on both the recipient of the donor of getting tested. And it's not any different. I mean that's the expectation by the FDA that the groups and the healthcare facilities and physicians that are performing standard donor fecal transplant that they basically abide by that.
Dr Lacy:
Maria, I like your analogy a lot. I'm going to start using that, that patients are very accepting of getting a blood transfusion or a kidney transplant or a lung transplant. This really is no different. We screen those donors, we make sure it's a really high quality sample. So can you tell us exactly how FMT is performed?
Dr Vazquez Roque:
Yes, so standard donor fecal transplant, in essence, there are some options of commercially available stool, but in Mayo Clinic in Florida specifically, we have our own biobank because we have our own standard stool donor. So we have samples available frozen, and essentially when a patient comes in, they meet criteria for a fecal transplant for recurrent C difficile. Then the patient has to do the preparation for any standard colonoscopy. We do the majority of our cases and deliver the stool through a colonoscopy. And so the patient's prep for any other colonoscopy gets sedation like any other colonoscopy. And essentially once we perform the procedure for the colonoscopy, we get to the cecum. We already have the stool prepared in specific prefilled syringes that are already prefilled with the donor stool. We put half of the stool in the terminal ileum and half of the stool in the cecum. And then we come out, we typically keep our patients a little bit longer in recovery to ensure we maximize the contact time of the stool with the colon. But that's pretty much it. I mean patients at this point are not continuing antibiotics for the C diff episode because obviously you don't want that, right? Because that could inactivate the live organisms that they just received. And so that's usually the path of the procedure and then just clinical monitoring and really seeing robust responses within 48 to 72 hours.
Dr Lacy:
Wonderful. And I think most patients are very accepting of performing a colonoscopy, but are there other options? Could we maybe use a tube into the stomach or small bowel like a nasogastric tube or a nasojejunal tube or those options and do they work as well as FMT via colonoscopy?
Dr Vazquez Roque:
Yeah, so great question. In the past doing fecal transplants through a nasal jegun tube or nasal gastric tube was a little bit more accepted. And actually one pivotal trial that was published in the New England Journal many years ago was actually done through nasal tubes in delivering the stool. I think the challenge I see when delivering stool so proximally is that because you are delivering a certain amount of stool, the distension that sometimes may be created in the stomach and the proximal small intestine can lead to patients to have episodes of vomiting, which obviously is not a great outcome when you've delivered stool directly into the stomach and the small intestine. And there is some data that has shown that the delivery of the stool directly into the colon is much more successful than an proximal delivery. We'll say though, that in patients that have post-surgical anatomy in their colons, we do sometimes have to go above with the scope, but we try to go really deep into the small intestines so we can deliver some of the stool in that fashion but not through a tube directly. So those are the circumstances that sometimes we may go above, but it would be with a scope and much more distal than what a tube can actually reach to minimize the risk of having vomiting or any unwanted side effects from that situation.
Dr Lacy:
Wonderful. So Maria, earlier you mentioned that the most common reason to perform FMT is recurrent C difficile colitis. When do you consider FMT for this patient population? Is a fail one course of an antibiotics or is it 2 or even more?
Dr Vazquez Roque:
Yeah, this is a great question. This is something I always talk with patients when we're using a standard donor stool sample, not anything else that's commercially available. There's strict guidelines established by the FDA because technically speaking, the standard donor fecal transplant is not approved by the FDA. We are able to perform it clinically under what's called enforcement discretion. And that requires for us clinicians that perform these procedures that the patient has to meet certain criteria including 2 or more recurrences of C difficile. Obviously recurrence, meaning within 8 weeks of completing the antibiotic for the initial episode of C diff, the patient recurs again. But the criteria for standard donor fecal transplants, it's 2 or more recurrences, 2 or more hospitalizations for C difficile infection. So for example, I cannot perform a standard donor fecal transplant if a patient's only on their first C difficile infection or sorry, recurrence. And so for that reason, it created limitations on how quickly someone could access standard donor fecal transplant, but doing it under that indication, meaning first recurrence is outside of what's been accepted by the FDA for clinicians to follow as a guideline for an indication.
Dr Lacy:
Wonderful. All right. So for our listeners, 2 or more recurrences, that's really the benchmark there. So what's the success rate of FMT for the treatment of recurrent c difficile colitis? Is it pretty good? And can you speak a little bit about patients and their attitudes? Can they get over the ick factor and would they do it again or was once enough if they don't?
Dr Vazquez Roque:
Yeah, you know what, Brian, it's a great question because oftentimes people obviously need to make decisions based on what the data is specifically with something like this, right? If they're going to accept stool from a complete stranger to them, obviously it needs to be very sustainable data. And the reality is that that's why standard donor fecal transplant really picked up since a 1958 onward is because the data of success became so overwhelmingly strong compared to when patients were having all these other complications and multiple hospitalizations, that the reality is that it's so strong, it's over 90% success rate, durable success, that it's hard to beat that, right? I'll mention though that it's important to understand that C difficile is a chronic infection, right? A standard donor fecal transplant is not a guarantee that you'll never in your lifetime ever have again a C diff infection.
But it's certainly almost a guarantee guarantees that this recurrence pattern that the patient may be going through, you actually stop that and give them some relief and hope that they're not going to be back in the hospital. And it's important to also highlight that the standard donor fecal transplant, when patients get that, at that point, they're at that second or third or fourth recurrence at that stage, the ability for a patient to respond to a standard of care antibiotic, meaning vancomycin or fidaxomicin becomes remarkably low. So at that point, when you look at the odds of success with a course of antibiotics, which could be anywhere between 10 to 20% at best, versus something that's 90% plus success, I mean, you can't beat that, right? That's a significant delta towards success of standard general fecal transplant. So I'll say this, yes, patients overcome the ick factor very quickly, especially when they've been through multiple recurrences.
I mean, they'll do essentially whatever it takes to really kind of get relief in having to deal with this because it creates a great deal of anxiety, especially since we have so much information in the tip of our hands of finding out what C diff is on Google or other search engines or social media, and it really creates a lot of anxiety. So people are really not, I think I would say the vast majority, if not all the patients I end up seeing in clinic, they're all in for standard donor fecal transplant. They're not complaining about it.
Dr Lacy:
Wonderful success rates of over 90% if medications could do that, right, would be amazing. So
Dr Vazquez Roque:
What about --it would be a very different world medically.
Dr Lacy:
It would be a different world, yeah. So let's think about predictors of success. I mean, if you're younger, are you more likely to respond than if you're older, if you're diabetic versus not diabetic? If you've had C diff 2 times versus 5 times, can we predict that response?
Dr Vazquez Roque:
Yeah, so it's a great question because these are kind of a couple things that I do talk to patients when I see them in clinic, but there’s been some retrospective studies to looking at what are the factors associated with failure of conventional or standard donor FMT, and those are going to be key, and critical ongoing use of antibiotics during or after the fecal transplant. If the patient has underlying inflammatory bowel disease, there's immune host factors that really put them at greater risk of failing a standard donor FMT; the quality of a colonoscopy preparation is poor. That really becomes a risk factor for the patient. The number of related hospitalizations is another one, Brian, that because if a patient gets hospitalized, that means that the C diff episode was in the severe category and that patient essentially that have more severe Cdiff are more likely to fail.
But I mean, and we just don't know what's that risk, individual risk by each of these factors. These are just factors that we know that are risk factors for failure. And also if a fecal transplant is performed in the inpatient setting, meaning that the patient's still hospitalized when they receive the fecal transplant, they're less likely to respond. And that probably is because that speaks to the severity, right? This is probably a patient that you're having to perform the fecal transplant inpatient because they're maybe not improving on standard of care antibiotics, i.e., vancomycin and fid. So I think that's obviously the risk factors for failure. But interestingly, the retrospective studies, and this was done by my colleague Sahil Khanna in Rochester, they did not see any difference with increasing age, immune suppression, or female sex. So that's fascinating, obviously, because we think that immune-suppressed patients actually carried greater failure or less chance of success, but that has not been seen in mid-analysis studies when they look at this individually and this data.
Dr Lacy:
It's wonderful information and actually really providing a lot of hope for patients who might have failed antibiotics. So I want to just circle back a little bit to FMT administration, and you've talked about all the many options to date, especially focusing on colonoscopy. But if people go online may read about FMT via capsules, can you give a fecal transplant through capsules? Does it work?
Dr Vazquez Roque:
Yeah, so you can, and previous bio banks would actually perform encapsulate the stools in gel caps that were sensitive, that they were resistant to the pH in the stomach. So they really pretty much opened more the distal small intestines, so it reached a colon. And so it's acceptable. There are some devices out there that are sold by other vendors where you can actually encapsulate your own pills, but it's not as widely acceptable because of the preparations. It's not that simple to do. And it's so much easier when you've already have the stool sample ready to go, but capsules are still available out there and biobanks as well may have them available to use, but they're a little bit more expensive from a biobank perspective when you purchase them because of the preparation and getting them into these specialized capsules that are resistant to the pH in the stomach.
Dr Lacy:
Wonderful. And so beyond C difficile colitis, because we've really been focusing on recurrent C difficile colitis, are there other diseases or disorders that can be treated with FMT?
Dr Vazquez Roque:
So that's a great question and it's an area of tremendous study, Brian, because C diff in itself, we understand it's when it's infection, there's active C diff disease and there's multiple when the patient's having recurrences at that point, we know that it's a disorder of the gut microbiome and pretty much restoring the diversity in the gut microbiome is really what clinches the deal, if you will. But there are other conditions that seem to be associated with the disorders of the gut microbiome themselves, right? Anything from neurologic disorders, movement disorders, even behavioral disorders. There's a lot of data coming out with cancer response to chemotherapy, immune checkpoint inhibitor colitis. So there's an emerging field in the space of the gut microbiome and how these disease states, the question really is to understand what came first, the chicken or the hen, is it the disordered microbiome that impacts certain disease states or the other way around?
But I can tell you for example, even though not FDA approved, but there's been data case reports of patients responding to standard donor conventional FMT with immune checkpoint inhibitor colitis if they're refractory to biologics and steroids. There's been case reports of patients succeeding with standard donor fecal transplant. So speaking to the role that fecal transplant may have in other disease states, but definitely much more research is needed to understand the underlying disease state, what is a fecal transplant modulating in this particular situation to ensure that it's safe for patients and ultimately hopefully get acceptance by the FDA. But right now under the enforcement discretion for conventional standard donor fecal transplant, it's only allowed for recurrent C difficile infection.
Dr Lacy:
Okay, well for our listeners, stay tuned. We'll likely hear more about this in the next two to three years. Very exciting in terms of research and clinical opportunities.
Maria, we really try to remain unbiased with these discussions and not focus on a specific product, but I know that many of our listeners will go to the internet and look up FMT and they will see that there are 2 commercial products on the market for the treatment of recurrent C difficile colitis beyond a standard stool transplant. One is called Vowst. The other is called Rebyota. Can you educate us briefly on what these products are and how they're similar or how they're different?
Dr Vazquez Roque:
Yeah, so it's a great question and very important for patients and listeners to know about this because up until 2022, we only had standard or conventional fecal transplant to treat patients with recurrent C diff. But ultimately because it's not FDA approved, I mean the need of having greater access for this industry came into play and 2 products came into the market, as you mentioned, Brian. One of them is Rebyota, which is essentially all of the products that I'm going to mention, which is the Rebyota and Vowst. The raw material where all these products come from, it's still human stool. So stool is still part of the makeup of these products. But in essence what they do is they just pretty much do extractions of specific microorganisms and prepare them like Rebyota. It's a microbial suspension that's delivered through enema and that is patient receives this treatment within 2 to 3 days after they've stopped their standard of care antibiotic for the C diff episode. It's an enema by gravity and it does not require preparation of the colon like for a colonoscopy.
And the success rate of Rebyota is hinging around 70% at 6 months and more data will follow with longer term data. But at least that tells us that 7 out of 10 patients that receive Rebyota do not have recurrent Cdiff up to 6 months mark. I will say this though, that all of these studies were not done in patients with IBD or high risk patients. So this is just a normal patient population in the community where they don't have high risk behaviors like IBD, for example, illnesses like IBD then fast forward to Vowst, so same idea, coming from human stool, but they encapsulate so Vowst gets encapsulated and its specific organisms in the capsules. Again, patients have to take it 2 to 3 days after finishing their standard of care antibiotic. There is a requirement of a bowel preparation, not the same as a colonoscopy, but a bottle of magnesium citrate to ensure that any residual antibiotic in the colon gets cleared out of the system so it doesn't inactivate the organisms.
And the has taken 4 pills daily over 3 consecutive days and that's it. Success rate has been reported up to 80% and that's sustained up to 12 months, which is great because obviously Vowst has some differences in that respect of making sure it's oral. Obviously the delivery is oral and patients don't get a new sedation, but there is a preparation that's required, but it gets shipped to the patient's home. And so that's how they're similar and how they're different. I mean the success rate of Vowst is 80% and Rebyota is 70%, clinically not that significantly different. And it really creates greater access for patients to get fecal transplant, whereas some centers may not have access to standard donor or conventional FMT.
Dr Lacy:
That's wonderful. Incredibly educational. It's nice to know that there are these other options available for people who may not be able to get a standard transplant. So Maria, I know you've thought a lot about this field, you're so involved in it and you've probably been thinking about where we're going in the future. Think about your pie in the sky dream. I mean 10 years from now, will we say that FMT is a standard of care to treat diabetes or to treat IBS or Crohn's disease? Where do you think we're going?
Dr Vazquez Roque:
Yeah, it's a great question, Brian. I think that as long as, I think the important piece to understand, so the short answer is there's a feature in other disorders that are associated with disordered microbiome. However, I think we need to understand at a more granular level all of these conditions that, like for example, you mentioned, I will mention this though, with inflammatory bowel disease, there's been various studies throughout the last 2 decades at least where they've used standard donor fecal transplant to treat Crohn's and ulcerative colitis. And there's really have not been, there's been just a response that's short duration. It's not long-term duration, which kind of speaks to the etiology of inflammatory bowel disease. There's a component that potentially is associated with the microbiome, but it's not strong enough necessarily because it's not sustained when patients receive fecal transplant. But other disorders, for example, immune checkpoint inhibitor colitis, where there's a significant signal from even clinical trials that were published recently in meetings at the ACG and DDW, and I think it's going to be really important to continue looking into diseases that have a really strong signal related to disordered microbiome.
Those are the diseases that we'll continue to see much more success of using fecal transplant. I think it's important to highlight, even though we see that it's stool, it really is trillions of microorganisms and it's not only bacteria, it's fungus, viruses, and parasites. And the vast majority of these do good things for the health of our colon. So we need that diversity of all these microorganisms to ensure that our colon cells are happy and that they're functioning well. And when we don't have enough of the diversity that the colon really yearns, that's when things start to kind of go south. And understanding the disease state clearly because they're not going to behave the same necessarily the same way patients may have C diff infection, may not be the same reason why someone else may get immune checkpoint colitis. So it's understanding those disease states better that will help drive future therapies when it comes to restoring the gut microbiome in an individual's colon.
Dr Lacy:
I like all those great teaching points. And for our patients, especially describing the gut microbiome, it's really a separate organ system that lives in this very delicate balance and sometimes it doesn't take much to disturb that delicate balance. So Maria, this has been a wonderful conversation. I've certainly learned an awful lot. I know our listeners have as well. Any last thoughts for our listeners?
Dr Vazquez Roque:
I think ultimately recognizing that our colon thrives with a diverse microbiome and not to think of microorganisms as bad things, but they're actually good things for the health of our colon and our gut in itself, but specifically our colon. So ensuring that if there ever is any issues with IC colitis, there are options and making sure that they understand it's not gloom and doom and there's obviously options to prevent these recurrences from happening, which I understand they can be very daunting for patients. So there's hope and I think that's the most important piece that there's hope.
Dr Lacy:
Wonderful. Maria, again, thank you so very much for lending your expertise on this important topic to our listeners on Apple, Spotify, and other streaming networks. I'm Brian Lacy, a professor of medicine at the Mayo Clinic in Jacksonville, Florida. You have been listening to Gut Check a podcast from the Gastroenterology Learning Network. Our guest today was Dr. Maria Vazquez Roque Associate Professor of Medicine for the Mayo Clinic in Jacksonville, Florida. I hope you found this just as enjoyable as I did, and I look forward to having you join us for future Gut Check podcasts. Stay well.
