The Healing Power of Poop: Fecal Microbiota Transplant in Ulcerative Colitis Patients
In the 21st Century, I’d like to think that our medical technology has advanced to the point that we can manage diseases precisely and elegantly. We truly have in some respects. We can sequence the human genome within a day or two, reduce new HIV infections with pre-exposure prophylaxis, and shoot lasers at kidney stones to remove them.
There are still some things we do in medicine that make me chuckle. One of them is the fecal microbiota transplant (FMT) where stool from a healthy donor is transferred to another individual to treat disease. The idea behind this bizarre practice is that the microorganisms (bacteria, fungi, viruses, etc.) living in the gut form a balanced healthy ecosystem, which causes or exacerbates certain diseases when it is out of balance. FMT restores balance to this ecosystem. This idea actually works wonderfully! FMT therapy has >90% success rate in treating diarrhea from Clostridium difficile infections, which are often caused by taking antibiotics resulting in an imbalanced microbial ecosystem. FMT has become the standard-of-care therapy for recurrent Clostridium difficile infections.
Naturally, doctors tested to see if FMT is effective in treating other diseases affecting the gut, such as ulcerative colitis (UC). In a large multi-center, double-blind, randomized trial with 85 patients, 44% of patients receiving FMT vs. 20% of patients receiving placebo had reduced symptoms. Why is it that only a subset of patients responds positively to FMT? Can we predict and identify these responders?
A research group at Cornell University sought to answer these important questions. Based on past studies showing that fungi in the gut play an important role, they hypothesized that fungi might contribute to responsiveness of FMT in UC patients. Cornell scientists compared fungi communities present before and after FMT treatments in responders vs. non-responders, and they discovered that responders had a higher abundance of a fungal species Candida before the FMT treatment. This means we could potentially use this as a biomarker to predict who will most likely respond to the FMT treatment!
What is the reason why preexisting Candida abundance in the gut is associated with positive clinical outcomes? Researchers proposed two hypotheses: 1) Candida present before the treatment could be exacerbating the disease and FMT treatment reduced their levels, or 2) Candida helps microbes in the FMT to colonize and restore balance to the gut ecosystem. Comparing Candida levels before and after FMT showed that it was reduced post-FMT, which suggests FMT might exert its effectiveness by reducing Candida. Furthermore, the group that received FMT had stable antibodies against Candida while the placebo group that did not receive FMT had significantly higher levels of antibodies against Candida. This suggests that Candida might be activating the inflammatory immune response, which exacerbates UC symptoms.
Indeed, the healing power of poop, while still a hazy mystery, shows great hope in treating chronic disease of the colon, and I can’t wait to see what FMT will help us accomplish!
By Than Kyaw
Clinical trial: https://www.sciencedirect.com/science/article/pii/S0140673617301824
Graphic from Leonardi et al describing their findings.