One therapy, many targets: redefining ulcerative colitis treatment through fecal microbiota transplantation

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease driven by a multifactorial interplay between gut microbiota dysbiosis, immune dysregulation, and epithelial barrier dysfunction. Accurate diagnosis and a deeper understanding of UC pathogenesis are essential for developing durable and mechanism-based therapies. Despite major advances, conventional treatments such as immunosuppressants and biologics often fail to achieve sustained remission and carry significant adverse effects, underscoring the need for novel, multi-target interventions. This review synthesizes current insights into UC pathogenesis, diagnostic approaches, and therapeutic strategies, with a particular focus on fecal microbiota transplantation (FMT) as a single therapy acting on multiple disease axes. By restoring microbial equilibrium, FMT can modulate host immunity and reinforce epithelial integrity, collectively promoting mucosal healing. We summarize mechanistic evidence, findings from preclinical and clinical studies, and key variables influencing FMT efficacy, including donor selection, preparation, and delivery routes. While evidence supports the therapeutic promise of FMT, challenges remain regarding standardization, long-term engraftment, and sustained safety. Nonetheless, FMT represents a transformative therapeutic platform that redefines UC treatment by bridging microbial restoration, immune modulation, and barrier repair. Future research should aim to refine FMT protocols and develop next-generation microbiota-based therapeutics, such as defined microbial consortia and live biotherapeutic products, to enable safer, more consistent, and personalized modulation of the gut ecosystem in UC.