Paul Feuerstadt, MD:Let’s change gears, we talked about antimicrobials that treat the vegetative phase. We talked about bezlotoxumab, which essentially binds toxin B and reduces the inflammatory response. But we have this black box, this dysbiotic state, this second piece that we need to be healthy to reduce future repeats. Tom, can you walk us through fecal microbiota transplantation in detail? Its mechanism of action and which patients can benefit from it?
Thomas Lodise, PharmD, PhD: As the name suggests, it involves the delivery of donor human stool to a person via a colonoscopy, enema, nasal nasogastric or nasoduodenal tube, or capsule, popularly known as a poop pill. It is prescribed to patients with debilitating GI infections, such as C difficile, and that is why we are here today. The thought is that you are restoring a balance in the microbiome. You want to get a better proportion of healthy versus unhealthy bacteria. We are trying to return to eubiosis from a dysbiotic state.
Paul Feuerstadt, MD:Essentially we take these defects – the Firmicutes and Bacteroidetes—and we fill them up with a full complement. What does this metabolically is the bile salt environment. The bile salt environment, we believe, has switches at this point C difficile on or off. We can switch to the appropriate complement of bacterial strains C difficile switch off and give the microbiome a chance to eradicate itself C difficile.
Bincy, we saw a stool transplant. It has been around for centuries, but in the last 10+ years mainly in clinical medicine. Are there any safety signals we need to be concerned about with fecal microbiota transplantation?
Bincy Abraham, MD, MS: Good question. Patients have asked us the same thing. The bottom line is that FMT [fecal microbiota transplantation] seems safe in the long term. Our biggest concern was the risk of infection. We bring in stool that has tons of bacteria in it, but we looked at that from the donors and ran rigorous testing to rule out any donor-derived infection. In fact, if done properly, there is a very small risk of transmission of infection with FMT.
Reviewing the literature, considering other potential long-term safety [concerns], some cities suggest a risk of weight gain. This had nothing to do with the donor’s BMI [body mass index]. Even the skinny donors contributed to weight gain in these patients. This happened in up to 10% of patients. This begs the question: is it a direct effect? Or could it be that the patients either lost weight or didn’t gain weight because they had repeated infections and were generally unhealthy? About 13% also had some reports of GI disorders such as chronic diarrhea or irritable bowel syndrome. We have to keep that in mind, but in terms of the long-term safety of FMT, no mortality has been identified.
Paul Feuerstadt, MD:It seems very safe. There are a few FDA reports looking at the transcription of various bacteria that have not been properly studied. You alluded to this, but whenever we consider a fecal microbiota transplant, or FMT, it’s important to think about where we’re getting the stool of origin, what the process they go through, and how comprehensive their process is.
Transcript edited for clarity