Fecal Microbial Transplant—A Follow-Up Discussion

So sometimes we move ourselves unknowing into a firestorm of controversy. And so it appears I have done with a recent video blog that we put out about fecal microbial transplant, which I'm very excited that the conversation has been initiated. But now I need to probably take the next step in understanding of what I was talking about. And to that I want to speak to this very recent paper that just appeared in a high tier journal, gastroenterology, in, in 2017. This would be volume 152, page 799 in 2017, talking about the effective use of sterile filtrates of fecal microbial materials from healthy donors. You recall this was the topic of my previous blog. This is a follow on to that topic because in this paper, which has done extraordinarily well, although it is only 5 patients, they have done speciation of each of these 5 patients after intervention on a daily basis to look at their microbiome and how they change after therapy and what was the therapy. Now these are all people with digestive disorders and diseases and the therapy they used was not fecal microbial transplant, but was the sterile filtrate of fecal material from healthy donors. Now what is a sterile filtrate? Just to remind you, it's where you take the fecal material, you homogenize it in a blender, you put it through a big filter to get all the debris out, then you start going to filters of smaller pore size, three different levels actually, until you get down to a filter that's 0.5 microns. So that means it would take out all bacteria. Only thing that we left in this fluid would be small molecules, some macromolecules, and maybe viruses, small viruses. But all of the living material would be taken out. In fact, if you take this filtrate and you put it on a nutrient rich plate, like an agar plate, it doesn't grow out anything. It's sterile. So historically we would say, or maybe think that this would be probably not effective for modulating either the microbiome or modulating the immune effects and the diseases associated with altered dysbiosis. Well, what do you find out in this article? All five of these patients had significant improvement, remarkable improvement, by the administration of this sterile filtrate with no living organisms in it. Now what that suggests, as the article points out, is that there may be a number of mechanisms as to how pre and probiotics work that are different than the way we used to think. It may not be that they just are taking over Real estate. In the GI microbiome, they may be producing certain kinds of things from their community of interaction, a network of bacteria that are interacting and communicating, that are producing secondary metabolites and other things that then go about doing what? Modifying the immune system of the host, their gut immune system, producing new molecules that may be immunological, activating tropic factors and things that stimulate proper immune function, which then when readministered back to an unhealthy host, an individual with a dysbiosis will restore the environment of the gut in such a way that the microbiome finds its own healthy position for that individual. Now why do I say that? Because in this particular paper it turned out that they didn't see the same change in all five individuals that were given the sterile filtrate. All of them changed remarkably. Their microbiomes changed and their condition improved, but they didn't change the same way. It was as if we each have our own microbiome that's unique to us for our health, that if we can find the right conditions of our immune system, the that that will be the point, the resting point, where our microbiome finds its healthy homeostasis. So rather than driving to an endpoint, which is to say let's get the right ratio of bacteroidetes to other organisms, rather than looking at a specific organism, let's look at the community that is established within the microbiome that then gives rise to the proper immunological crosstalk with the host. So if the host's immune system is compromised, then that can change the microbiome. If the microbiome is disrupted, it can cause a change in the host. So it's host immune system, so it's finding the right complex that gives rise to this homeostasis. Now I think this is very interesting because when they did analysis of that filtrate, they found all sorts of different molecular weight species that were a product of bacterial metabolism and even immune function and metabolism of the human host in that filtrate. But they also found something that we often don't consider important and that is bacteriophages. Bacteriophages, as you know, are viruses that are extraordinarily important for controlling bacteria. They're lethal to bacteria. So they sit on the surface of bacteria and they, they take care of bacteria. So they're bacteriocyl many of these bacteriophages. And it turns out that these bacteriophages are found in sterile filtrate because when you test for them, you will find they were present in all the filtrates that were used in these five patients. So there may be much more to this story than we used to think about. Probiotics and prebiotics and synbiotics. It may be establishing the network effect of the right type of bacteria, speaking one to the other, along with bacteriophages, along with immune active small molecules that gives rise to a matrix effect that then in the gut creates the right environment for the microbiome to be associated with health. So I think that this is opening up a whole new chapter in our understanding as to both how to assess health at the microbiome level and how to engage in therapeutic intervention that would add back or contribute these kinds of agents that would establish the appropriate homeostasin for that person's healthy microbiome. Exciting new chapter of our story and one that I think really takes us beyond just a single kind of thought of this probiotic is going to be good for everyone to really look at selective speciation and selective personalization of therapy based upon establishing this healthy microbiome. Really exciting stuff.