Fecal Microbial Transplant: Innovative Research and Therapeutic Potential

So fecal microbial transplant or fmt, really an exciting topic. Well it actually is an exciting topic quite honestly because it really brings to bear the importance of the microbiome as it relates to systemic health. And as you probably know, this started off with the suggestion from some anecdotal studies that have been done actually in Sweden associated with Karolinska Institute that enemas that were then administering homogenate of stool from healthy donors was able to reduce the infection of Clostridium difficile and could have a positive benefit then on overall systemic health as it relates to some of these intestinal infectious organisms. So that was a very interesting kind of, aha, maybe looking a little bit crude at first, but the construct was by re establishing the appropriate bacteria in the colon that you could then have this positive effect on the immune function of the gut. Well, it's gone way beyond that now over the last 10 years with many, many more clinical intervention trials and more standardized procedures. And I had the privilege just recently when I was down in Australia at a conference on the microbiome to meet Thomas Barodi. Now Dr. Barodi is a professor of gastroenterology in New South Wales at the Medical School University there and has done probably more controlled studies in FMT fecal microbial transplant than any other human being. You probably are familiar with his most recent paper because we did discuss it briefly in a previous video blog. This appeared actually in the Lancet as a featured article. Actually it was described on the COVID of that issue of the Lancet. This was the March 25, 2017 issue of the Lancet entitled Multi Donor Intensive Fecal Microbial Transplantation for Active Ulcerative Colitis. A randomized placebo controlled trial. So we've moved beyond C. Difficile in this study to ulcerative colitis. Now this is becoming ever then more interesting as it relates to the potential multiple clinical conditions for which FMT might be useful. And in fact there's an editorial that follows that particular article in the Lancet that's really powerful. That's entitled Is Intensity the solution for FMT in Ulcerative Colitis? In which they're talking about what's the dose of these organisms that you need to administer in order to get a positive clinical outcome. And then the question is obviously what's the way that these should best be administered from the south up by enema or from the north down by oral administration in a freeze dried capsule form. So there's all sorts of interesting different ways of thinking about this technology. But then I had the privilege of talking to Dr. Borody while we were together at the Australian conference and he brought up a point that I think is a real aha. He said, jeff, are you familiar with this paper that was published in gastroenterology in 2007? That's the journal Gastroenterology, as you know, one of the premier journals in gastrointestinal medicine. And it was a study that was done by a series of collaborative investigators actually from University of Kiel in Germany, from the gastroenterology department in collaboration with a investigator at the University of California San Diego Medical School. And he said, this really has changed the whole complexion of FMT as it relates to a go forward potential therapy. And I said, wow, that's a dramatic statement. What is this study? And he says, well, here's the citation, look it up. You're going to find it extraordinarily interesting. And interesting it is. The title of the paper is Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients with C. Difficile Infection. Now, I want to emphasize sterile fecal filtrates. Now what does that mean? That means taking the stool from healthy donors, putting it through a filtration system to take out all the living organisms, even the viruses. So a very small pore sized filtration and taking that sterile filtrate that has no viruses or bacteria in it and administering that once it's been dried down, lyophill eyes, administering that to humans who have C. Difficile to see if the filtrate with no living organisms in it can have an effect upon their gastrointestinal disorder. And the answer is yes. In a small clinical pilot trial, this was done again in Germany with individuals who had C. Difficile by administering orally the lyophilized extract of the supernate of this filtrate. Basically it was found that they had remission of their C. Difficile. Now what does that say? That says that it's not the living organism in and itself, it's the microbiological machine that is represented by the complex of these organisms that ferment and metabolize in the gut. Specific stuff that comes from our diet that produces secondary byproducts that then are soluble products, not the bacteria themselves, but soluble products from their metabolism that are a bunch of families of small molecules and proteinoid molecules that then can be concentrated, isolated and ultimately given as a kind of a therapeutic with multiple biological activities within it as a consequence of the community of those organisms in a healthy donor that were metabolizing their foods in the colon in such a way as to produce that array of molecules. Now, that's a very powerful concept because it says there's not like one bug, one bacterium that's going to treat C. Difficile. What it says is it's probably an ecological principle of a variety of bacteria working together in the gut that then creates an environment whereby undigested food materials that could be like plants, cellulose materials, for instance, that then give rise to a series of metabolites for which then the immune system of our body then responds favorably so as to reduce infection. So I think we need to stay tuned to this. This is a very big step forward in maybe making FMT more accessible, because probably more people would be interested in lyophilized sterile filtrate as a therapeutic than taking somebody else's stools as a therapeutic. So I think that there's lots to learn, but it certainly suggests that the ecology of our microbiome, not just one bacterium, is what's really going to be important to understand how it then influences our body's immune system. So, by the way, those of you that want to follow up on this citation, just to check to see if I'm accurately portraying it, it's Gastroenterology, March of 2017, Volume 152, Page 799. I think this is a sign of things to come.