Background and aimsFecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for ulcerative colitis (UC). This single-center retrospective cohort study evaluated the clinical effectiveness and safety of an optimized FMT protocol, in which donor bacteria were concentrated by tangential-flow micropore membrane filtration and delivered after pre-FMT antibiotic preconditioning, as adjunctive therapy in adults with mild-to-moderate UC.MethodsWe analyzed prospectively collected data from 156 patients with mild-to-moderate active UC treated between December 2022 and December 2024. Treatment allocation was determined by a shared clinical decision between the gastroenterologist and patient based on disease severity, prior medication exposure, and patient preference. Patients were grouped into four pre-specified treatment strata: aminosalicylates alone (Group A, n = 42), aminosalicylates plus corticosteroids/immunosuppressants (Group B, n = 38), aminosalicylates plus FMT (Group FMT1, n = 40), and aminosalicylates plus corticosteroids/immunosuppressants plus FMT (Group FMT2, n = 36). Donor stools were processed using a validated tangential-flow 0.22-μm membrane filtration workflow that retains and concentrates viable bacteria in the retentate while clearing soluble metabolites and host debris in the permeate. Confounding was addressed using multivariable logistic regression and inverse probability of treatment weighting (IPTW) as a sensitivity analysis. The primary outcome was clinical response at 12 weeks; effect sizes are reported as risk differences with 95% confidence intervals.ResultsClinical response rates at 12 weeks were 31.0% (Group A), 52.6% (Group B), 72.5% (Group FMT1), and 77.8% (Group FMT2). Clinical remission rates were 19.0%, 34.2%, 55.0%, and 61.1%, respectively. FMT-containing regimens were associated with higher response and remission than aminosalicylates alone (risk difference for response: 41.5%, 95% CI 22.7–60.3% for FMT1 vs. A; 46.8%, 95% CI 28.0–65.6% for FMT2 vs. A; both P < 0.001). Microbiome analysis using 16S rRNA gene sequencing showed that responders had increased Bacteroides-related amplicon sequence variants and increased alpha diversity comparable to donor profiles, while non-responders maintained dysbiotic profiles. Adverse events were mild and comparable across all groups.ConclusionsIn this retrospective cohort, an optimized FMT protocol using membrane-filtered bacterial concentrates was associated with higher rates of clinical response, clinical remission and endoscopic improvement at 12 weeks compared with conventional therapy, with an acceptable short-term safety profile. Given the observational design, these findings should be interpreted as hypothesis-generating and require confirmation in randomized controlled trials.