Microbiota Therapeutics – Additional

(non-C. difficile) Treatment Areas

C. difficile infection that does not respond to standard therapies (antibiotics) is the only indication for which the FDA currently allows clinical use of IMT outside of clinical trials. The only other mechanism for which the FDA may make an allowance is compassionate treatment of a single patient or a small group of patients. However, the FDA allowance must satisfy two essential criteria. The condition must be life threatening and all standard therapies have been exhausted.

Definitely NOT! First, we need to consider the dosing regimen. The indigenous gut microbes of patients with C. difficile infections that failed all antibiotic treatments have been decimated by all those antibiotics. A single dose of donor microbes restores normal microbial composition of stool of patients because there are few competitor microbes. However, the dosing regimen for other conditions generally needs to be much more intense in order to achieve measurable change. This is because the new microbes have to displace the entrenched resident microbes. Second, there is the question of donor matching. When we treat patients with C. difficile infections, our simple objective is to restore a ‘healthy’ microbial composition in the gut. Matching is not a concern in this situation and our donor selection focuses mainly on donor health. However, we believe that more sophisticated selection of donor microbes, tailor-made for specific diseases, is needed for most conditions other than C. difficile infections that are of interest to patients. Indeed, this is what we are trying in some of our clinical trials. However, the microbiome science is still very young and we don’t have microbiome-based diagnostic tests to select the right donors for non-C. difficile indications. Therefore, basic research and clinical trials will remain critical if we’re ever to make progress in this field.

Probiotics are not therapeutics. They are not intended to treat, mitigate, or prevent disease. They have not been formally tested to treat any disease. In fact, manufacturers are disincentivized to rigorously test whether probiotics help any diseases because doing so risks their products being classified as drugs and that would prohibit sales as dietary supplements. Marketing of these products can be very seductive, but it should not be confused with very specific claims that are associated with true therapeutics. We don’t recommend probiotics for most clinical indications.

No one knows exactly what causes inflammatory bowel diseases (IBD), but the current thinking is that it results from an overactive immune system to the gut bacteria in a genetically susceptible person. This is not an infection, where one organism overgrows in a place where it shouldn’t be, rather this is an inappropriate immune response to our own gut bacteria. As we don’t know exactly what triggers IBD, we typically focus treatment on decreasing the overactive immune system. However, as our ability to study the microbiota (gut bacteria) has increased, we are learning that bacteria (or other microorganisms or their products) may trigger or perpetuate inflammation.

If the gut bacteria are involved in triggering the immune system, then altering the gut bacteria may impact the immune response.  Antibiotics are one way to alter the gut bacteria. However antibiotics kill off all bacteria (healthy ones and potentially harmful ones as well).  Overall antibiotics result in decreasing the diversity of the gut bacteria.  This is a problem, because in IBD the diversity of microorganisms is already decreased.  Sometimes antibiotics can be helpful in controlling symptoms, or managing complications of IBD, but as of now antibiotics alone are not a long term treatment for managing IBD.

Our ultimate goal is to develop therapies directed at restoring healthy gut bacteria that can treat the inflammation and symptoms for people with IBD. In some cases this might be replacing the gut bacteria (intestinal microbiota transplant), but in other cases it might involve dietary changes to promote healthy gut bacteria. As we learn more, we are hopeful that one day we might be able to use these changes to cure IBD.

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