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According to the Centers for Disease Control and Prevention, Clostridioides difficile infection is responsible for almost half a million illnesses in the U.S. each year, with a 20% recurrence rate. C. difficile pathogens are highly opportunistic, and can dominate the intestinal environment after an event that disrupts the normal gut flora, such as a course of antibiotics.  

A lot of excitement has been generated around an innovative treatment called “fecal microbiota transplantation (FMT),”  which has been able to resolve 80-90% of recurrent C. difficile infections. FMT is exactly as it sounds: stool donor is transplanted into the colon of a recipient (Link to informative video here.)  However, as with most things, there are many challenges to evaluating FMT as a treatment for disease, and many considerations that need to be made relating to product design and treatment administration. 

Below, I summarize in a casual manner, a paper published in Cell Host & Microbe on February 12, 2020 by Markey, van den Brink, and Peled:

Existing challenges to the field include:

  • Due to high individual variability, it is difficult to define an “optimally healthy” gut microbial state, and similarly difficult to define a singular disease-associated gut microbial state. 
    • We also don’t know how, or the extent to which, disease-associated microbes interact with their host to cause or contribute to the disease. 
  • The success of FMT is dependent on the recipient’s pre-existing gut environment, though upon which characteristics of the environment, are yet unclear.
    • Along these lines, some patients have even developed infections resulting from FMT treatment.

Product design:
Currently, there are multiple strategies for FMT, ranging from 
unmanipulated stool (from your past, healthier self, from a close relative, or from a stool bank) → stool pooled from multiple donors (more diversity, but is that a good thing?) → stool filtrates, where only secreted factors from the bacteria are used → probiotics, or specific strains of bacteria that may be therapeutically beneficial. 

Clearly, simpler approaches (stool filtrates and probiotics) are desirable for the purposes of creating a product that can be easily mass-produced and screened for quality. However, these approaches rely on both identifying certain bacterial taxa and the mechanisms behind how these bacterial taxa affect a specific disease state.

Treatment administration:
Next, there is the question of whether the FMT product will have its intended effects in the recipient, when there is such high individual variability in the gut environment. What factors regulate the success of FMT in some but not others? Do we need to pre-treat the recipient in some way, perhaps via a dose of antibiotics, so the recipient will respond better to the FMT? 

My opinion ( as a trainee) is that if FMT will ever be approved as a viable treatment for illnesses other than C. diff infection, we need more descriptive studies detailing which subsets of bacteria are present in healthy individuals but perhaps absent in individuals with particular condition X (which would be nice and easy), or may be more abundant in healthy individuals than in individuals with particular condition X. We then need to perform experiments to discover which, or which combinations of these subsets, can cause aspects of that condition to appear. After that, we can zoom in, focusing on knowing more about how these bacteria interact in the gut community, and what sorts of factors they secrete, and how these factors affect their host. 

I predict that, within this decade, FMT in some sort of solid product design format, will be approved as treatment for ulcerative colitis (it’s already showing promise in some studies). After that, who knows? The possibilities for poop are endless.

Assemble, gut microbiome researchers!

the microbepipettor