Intensive fecal microbiota transplant (FMT) from multiple donors led to clinical remission of active ulcerative colitis in a recent trial.
Researchers at three Australian hospitals performed a randomized, double-blind, placebo-controlled trial in which patients with active ulcerative colitis, defined as a Mayo score of 4 to 10, were assigned in a 1:1 ratio to receive FMT infusions from three to seven unrelated donors or placebo infusions into the cecum or terminal ileum via endoscopy. (The Mayo score assesses severity of ulcerative colitis by evaluating stool frequency, rectal bleeding, mucosal appearance on endoscopy, and physician rating of disease activity on a scale of 0 to 12, with a higher score indicating more severe disease.) Beginning the next day, all patients then received enemas five days per week for eight weeks, five days on and two days off. The study's primary outcome was clinical remission without steroids, confirmed by endoscopy at week 8 (Mayo score of ≤2, all subscores of ≤1, and ≥1-point reduction in endoscopy subscore). The researchers also assessed associated microbial changes with 16S rRNA stool analysis. The study results were published online Feb. 14 by The Lancet.
A total of 85 patients were enrolled in the trial from November 2013 to May 2015. Of these, four patients were excluded because they never received the study treatment; therefore, 41 patients in the FMT group and 40 patients in the placebo group contributed to the study analysis. Most patients (54% in the FMT group and 63% in the placebo group) were men, and most (66% and 68%) were white. Mean age in each group was 35.6 years and 35.4 years, respectively.
Eleven of 41 patients in the FMT group and three of 40 patients in the placebo group achieved the primary outcome at week 8 (27% vs. 8%; risk ratio, 3.6; 95% CI, 1.1 to 11.9; P=0.021). Thirty-two of 41 patients in the FMT group (78%) and 33 of 40 patients in the placebo group (83%) reported adverse events, most of which were self-limiting GI issues. Serious adverse events were reported in two patients in the FMT group and one patient in the placebo group. The researchers noted that FMT led to increased and persistent microbial diversity and that some bacterial taxa appeared to be associated with clinical outcomes (patients with Fusobacterium and Sutterella spp, for example, appeared less likely to achieve remission).
The authors noted that intensive FMT is difficult to perform and that it is unclear whether it is suitable in patients with severe disease, among other limitations. However, they concluded that according to their results, this treatment shows promise for ulcerative colitis. They called for additional studies on long-term outcomes and microbiological mechanisms. “In particular, identification of specific bacteria associated with a positive or negative response, and matching donors and recipients based on microbial profiles, could lead to improved personalised faecal microbiota transplantation or defined microbial consortia manipulation,” they wrote.
The author of an accompanying comment pointed out that more patients with mild disease were assigned to the placebo group than to FMT and that one particular donor appeared to be associated with better outcomes. In addition, she wrote, FMT did not appear to improve quality of life, perhaps because of the intensity of the treatment. However, the comment author noted that the study offered potential support for intensive therapy over an extended time period for ulcerative colitis, in contrast to colitis associated with Clostridium difficile infection, which usually requires a single FMT procedure. She called for future studies to determine a maintenance protocol for ulcerative colitis and to determine the optimum composition of FMT enemas, noting, however, that “the ultimate aim will be to achieve the best transplant without the need for actual donors.”