Faecal microbiota transplantation (FMT) is a therapy targeting the gut microbiome with the strongest evidence for efficacy in the treatment of recurrent Clostridium difficile infection. Although gut microbiota dysbiosis is involved in the pathogenesis of ulcerative colitis, the role of FMT as a therapy for it is still controversial as the two big randomised controlled trials done previously (here; here) had contradictory results.
A recent randomised placebo-controlled trial, led by Prof. Thomas Borody from the Centre for Digestive Diseases in Sydney (Australia), has found that faecal microbiota transplantation induces clinical remission and endoscopic improvement in patients with active ulcerative colitis.
The researchers conducted a multicentre, double-blind, randomised, placebo-controlled trial at three Australian hospitals (St Vincent’s Hospital, Sydney; Bankstown-Lidcombe Hospital, Sydney; and Nambour General Hospital, Nambour). Patients aged 18-75 years with clinically and endoscopically active ulcerative colitis (with a total Mayo score of 4-10) for greater than 3 months were randomly allocated in a 1:1 ratio to either FMT (n = 41) or placebo (n = 40) colonoscopic infusion. Both interventions (experimental and control) consisted of enema administration 5 days per week for 8 weeks. FMT enemas were each derived from between three and seven unrelated donors. The intensity of treatment and the use of a total of 40 multidonor enemas is a key feature that distinguished this trial from previous studies (here; here) of FMT in ulcerative colitis, which utilised single-donor infusions and a more limited treatment schedule. The primary outcome was steroid-free clinical remission with endoscopic remission or response (total Mayo score £ 2, with all subscores £ 1, and ³ 1 point reduction from baseline in endoscopy subscore) at week 8. Gut microbial changes were also analysed by 16S ribosomal RNA (rRNA) stool analysis.
At week 8, steroid-free clinical remission and endoscopic remission or response were achieved in 11 (27%) of 41 patients allocated FMT versus three (8%) of 40 who were assigned placebo. When it came to secondary outcomes, at week 8, steroid-free clinical remission (combined Mayo subscores of £1 for rectal bleeding plus stool frequency) was achieved in 18 (44%) of 41 patients assigned FMT compared with eight (20%) of 40 allocated placebo. Steroid-free clinical response (decrease of ³ 3 points or ³ 50% reduction from baseline or both in combined Mayo subscores for rectal bleeding plus stool frequency) was achieved, respectively, by 22 (54%) of 41 and nine (23%) of 40 patients. Steroid-free endoscopic response (Mayo endoscopy subscore £ 1, with ³ 1 point reduction from baseline) was noted in 13 (32%) of 41 patients assigned FMT compared with four (10%) of 40 allocated placebo. However, steroid-free endoscopic remission (Mayo endoscopy subscore 0) did not differ between treatment groups.
The most common adverse events were self-limiting gastrointestinal complaints and were reported by 32 (78%) of 41 patients allocated FMT and 33 (83%) of 40 who were assigned placebo. There was no significant difference in number or type of adverse events between study groups. Besides this, six serious adverse events occurred during study treatment: two in patients assigned FMT, one in a patient allocated placebo, and three in patients who progressed to open-label FMT.
Regarding the microbial changes associated with treatments, microbial diversity increased significantly compared to baseline in all patients treated with FMT, at 4 weeks and 8 weeks, and persisted 8 weeks after therapy completion. Interestingly, Fusobacterium spp and Sutterella spp were associated with lack of remission. Fusobacterium genus was previously noted to be involved in ulcerative colitis pathogenesis with an increased capacity for invasion in patients with inflammatory bowel disease compared to healthy controls.
In conclusion, multidonor intensive FMT induces steroid-free clinical remission and endoscopic improvement in patients with active ulcerative colitis compared to placebo and is associated with distinct microbial changes that relate to outcome. These results open confirm the use of FMT as a possible new complementary treatment option to currently available immune-based therapies for patients with ulcerative colitis.
Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017; doi: 10.1016/S0140-6736(17)30182-4.
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