Efficacy of different modalities of faecal microbiota transplantation in ulcerative colitis: systematic review and network meta-analysis

Abstract

Background: While several small sample size randomized controlled trials suggested the superiority of faecal microbiota transplantation (FMT) over placebo in ulcerative colitis (UC), the most effective modality to perform FMT remains unknown.

Objectives: To compare the efficacy of different modalities of FMT to induce clinical remission in patients with UC.

Data sources and methods: We performed a systematic review and network analysis (sources: MEDLINE, Embase, Cochrane CENTRAL; random effects model) of randomized controlled trials including at least one arm of FMT in adult patients with active UC. The primary endpoint, that is, clinical remission (total Mayo score ⩽2 with Mayo endoscopic score ⩽1), was assessed between weeks 6 and 12. Results are expressed as relative risks with 95% confidence intervals, adjusted for bowel cleansing and pre-FMT antibiotics. Ranking of FMT modalities was calculated as their surface under the cumulative ranking (SUCRA).

Results: Among the 12 selected studies, patients were exclusively bio-naïve in 4 studies (4/12), while between 9% and 32% had prior biologics exposure in the other trials. The risk of bias was low across all domains in seven studies. Contrary to upper gastrointestinal tract (GI) FMT (Relative risk (RR) = 1.1 (0.2-7.7)), oral capsule (RR = 7.1 (1.8-33.3)), lower GI FMT (RR = 4.5 (1.7-12.5) and combination of both (RR = 12.5 (2.1-100)) are more effective than placebo to induce clinical remission. The combination of lower GI FMT and oral capsule was significantly more effective than upper GI FMT to induce clinical remission (RR = 10.7 (1.1-104.2)). Combination of lower GI FMT and oral capsule ranked the highest for the induction of clinical remission (SUCRA = 0.93). Multidonor FMT did not perform better than single donor FMT. Autologous FMT ranked lower than placebo (SUCRA = 0.12 vs 0.22).

Conclusion: The combination of lower GI and oral capsule FMT seems to be the best modality of FMT for patients with UC. In clinical trials, autologous FMT should be avoided due to a potential detrimental effect.

Trial registration: PROSPERO registration number: CRD42023385511.

Keywords: delivery route; faecal microbiota transplantation; randomized controlled trial; ulcerative colitis.

Figure 1.

Search strategy according to PRISMA guidelines.

Figure 2.

Network plot of the meta-analysis.

Figure 3.

SUCRA for FMT modalities to induce clinical remission in patients with UC. (A higher SUCRA score means a higher ranking for efficacy outcomes.) FMT, faecal microbiota transplantation; SUCRA, surface under the cumulative ranking; UC, ulcerative colitis.

Figure 4.

SUCRA for FMT modalities to induce clinical remission in patients with UC, distinguishing between FMT from pooled samples from multiple donors and single donors. (A higher SUCRA score means a higher ranking for efficacy outcomes.) FMT, faecal microbiota transplantation; SUCRA, surface under the cumulative ranking; UC, ulcerative colitis.