Clinical and microbiological studies of faecal microbiota transplantation in ulcerative colitis

Introduction: While the gastrointestinal (GI) microbiota plays a critical role in ulcerative colitis (UC) pathogenesis, UC treatments are predominantly immunologically based. Traditional methods of therapeutic microbial manipulation such as antibiotics and probiotics demonstrate at most modest benefit. Faecal microbiota transplantation (FMT), the introduction of faecal suspension derived from a healthy donor(s) into the GI tract of a diseased individual, has the advantage that it provides the full microbiota spectrum from a healthy individual. Given the remarkable efficacy of FMT in Clostridium difficile colitis, FMT may be of value in UC. AIM: To determine the efficacy and safety of multi-donor FMT in UC and the effect of FMT on the resident microbiota of recipient patients. METHODS: A multi-centre, randomised, double-blind, placebo-controlled trial of multi-donor FMT in UC was conducted, coupled with microbial analyses including 16S rDNA high throughput pyrosequencing to investigate the underlying microbiological basis. To establish the benefit of FMT in IBD and identify predictors of improved outcomes, a systematic review and meta-analysis was performed. RESULTS: Faecal donor recruitment was challenging (10% success rate), with a significant proportion failing stool testing due to GI parasites. Multi-donor FMT definitively demonstrated efficacy in UC, meeting the primary endpoint of steroid free clinical remission and endoscopic remission or response (11/41 [27%] of FMT-treated patients vs 3/40 [8%] placebo-treated patients; RR 3.6; p=0.021) along with most secondary endpoints. No significant difference in number or type of adverse events was noted between FMT and placebo, these being primarily self-limiting GI complaints. Recipient microbial diversity increased with, and persisted after FMT, with those achieving primary outcome displaying greater diversity at baseline, during and 8-weeks post FMT. Several bacterial taxa were associated with clinical outcome. Meta-analysis confirmed FMT was effective in UC, particularly with multiple infusions and lower GI tract administration, but long-term durability and safety remain unclear. CONCLUSION: These studies demonstrate FMT is an effective treatment for UC, with satisfactory short-term safety. FMT induces durable changes in the intestinal microbiota profile of UC patients, with increased microbial diversity, differential abundance of bacterial taxa, and changes correlating with therapeutic outcomes