Fecal microbiota transplantation in ulcerative colitis: mucosal immune mechanisms and precision microbiota therapy

Fecal microbiota transplantation (FMT) has emerged as an investigational microbiota-targeted strategy for ulcerative colitis (UC), aiming to restore dysbiotic gut ecosystems and microbiota-host homeostasis. Mechanistic studies suggest that FMT may reshape microbial community structure, enrich short-chain fatty acid-producing bacteria, remodel bile acid and tryptophan-aryl hydrocarbon signaling, enhance epithelial barrier integrity, and regulate mucosal immunity, including Th17/Treg balance, IgA-associated responses, macrophage reprogramming, IL-10/IL-22 signaling, and neutrophil extracellular trap formation. Randomized controlled trials indicate that FMT can induce clinical and endoscopic remission in selected patients with UC, particularly when administered through the lower gastrointestinal route and using multi-donor or optimized regimens. Current guidelines do not recommend conventional FMT as routine therapy for UC outside clinical trials, reflecting the heterogeneity and low certainty of available evidence. However, its efficacy appears limited in moderate-to-severe or biologic-refractory disease, underscoring the importance of host inflammatory burden and recipient ecological receptivity. Personalized strategies, including donor-recipient functional matching, dietary modulation, combination therapy, and next-generation microbiota therapeutics, may improve response and safety but require prospective validation. This review integrates microbiota-metabolite-barrier-immune mechanisms with clinical evidence to define where FMT may be useful, where its benefit appears limited, and how future studies can move the field toward precision microbiota therapy in UC.