Improving ulcerative colitis prospects through Fecal Microbiota Transplantation: atypical donor microbiota could boost success rate

Fecal microbiota transplantation (FMT) has been used with variable success in the treatment of ulcerative colitis (UC), and efforts to improve its efficacy, notably pursuing the search for high-performing donor microbiota, very much remain a matter of trial and error. We recently proposed a conceptual model of the intestinal ecosystem that could explain the variable success of FMT, while predicting that an atypical donor microbiota could improve FMT outcomes. Here we provide experimental support for this prediction.In a rat model, we induced a transition of the intestinal ecosystem to an alternative stable state characterized by chronic low-grade inflammation and dysbiosis. We examined if autologous FMT, as a model for the use of an ideal recipient-matched healthy microbiota, or allogenic FMT could favor the restoration of a healthy ecosystem.Autologous FMT did not enhance the restoration of a healthy microbiota compared to a control group without FMT. In contrast, the microbiota from one of two allogenic donor strains used turned out to be remarkably successful in the restoration of a healthy microbiota, in some cases accompanied by a healthy distal colon histology.The results support our earlier prediction that an atypical donor microbiota could boost FMT success and suggest a procedure that may assist donor microbiota selection. They further show that in order to advance our understanding of what constitutes a high-performing donor microbiota, the results of FMT should be evaluated at the level of the recipient's microbiota as much as clinical outcome.