S1932 Microbiota-Targeted Therapies in Biologic-Refractory Ulcerative Colitis: A Systematic Review and Meta-Analysis

Introduction: The safety and efficacy of microbiota-targeted therapies (MTT), including fecal microbiota transplantation (FMT), probiotics, and postbiotics, for ulcerative colitis (UC) have been investigated in adults (≥18 years) and have shown potential in restoring intestinal balance. However, their role in biologic-refractory UC is controversial. Biological refractory ulcerative colitis is a type of ulcerative colitis that doesn’t respond to biological treatment. We conducted this systematic review and meta-analysis to evaluate the safety and effectiveness of MTT in adult patients with biologic-refractory ulcerative colitis, incorporating the latest clinical trial evidence. Methods: We conducted a systematic search up to May 2025 in PubMed, Cochrane Library, Scopus, Embase, and ClinicalTrials.gov, following PRISMA guidelines. Study selection was done using Rayyan, and data on clinical and endoscopic outcomes and adverse events were extracted into Excel. Meta-analysis was performed using RevMan 5.4 with a random-effects model. Heterogeneity was assessed using I² and P-values, with sensitivity analyses conducted to test the robustness of findings. Results: We included 10 studies involving total of 491 patients. MTT significantly improved clinical remission compared to control (RR = 2.04; 95% CI: 1.18–3.54; P = 0.01), with results remaining robust after excluding a high-weight outlier (RR = 2.12; 95% CI: 1.43–3.15; P = 0.0002). Clinical response was also significantly higher in the MTT group (RR = 1.94; 95% CI: 1.29–2.90; P = 0.001), as was endoscopic remission (RR = 2.36; 95% CI: 1.39–4.03; P = 0.002). Total adverse events did not differ significantly between groups (RR = 0.92; 95% CI: 0.76–1.11; P = 0.39), suggesting a comparable safety profile. Heterogeneity was low to moderate across outcomes, except for initial clinical remission (I² = 68%), which improved notably in sensitivity analysis (I² = 10%). Conclusion: Our systematic review and meta-analysis shows that microbiota-targeted therapies are safe and effective in inducing clinical and endoscopic remission in patients with biologic-refractory ulcerative colitis, without increasing total adverse events. However, the heterogeneity of interventions and relatively small study populations warrant further large-scale trials to determine optimal treatment strategies and assess long-term outcomes.