The Gut Microbiome in Pouchitis: A Narrative Review of Pathogenesis and Therapeutic Modulation

Pouchitis is the most common long-term complication following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), with a cumulative prevalence of up to 50% within the first two years after IPAA surgery. Accumulating evidence implicates gut microbial dysbiosis in the pathogenesis of pouch inflammation, supported by characteristic microbial alterations and the clinical responsiveness of pouchitis to microbiota-directed therapies such as antibiotics and probiotics. This narrative review synthesizes evidence mainly published in the last decade on microbiota alterations in pouchitis, the mechanisms of microbiota-host interactions that may contribute to inflammation, and the clinical evidence linking the gut microbiota to disease development and progression. Therapeutic strategies for modulating the pouch microbiota, including probiotics, prebiotics, dietary interventions, antibiotics, and fecal microbiota transplantation, are critically evaluated. Finally, future directions in multi-omics profiling, precision microbiome medicine, and next-generation live biotherapeutics are discussed. Overall, current evidence supports antibiotics as the first-line treatment for pouchitis, although it does not restore microbial eubiosis. Among microbiota-targeted interventions, the eight-strain De Simone formulation has the strongest evidence for prevention, whereas faecal microbiota transplantation remains investigational and is not currently supported outside clinical trials. Further research integrating multi-omics and microbiome profiling is needed to better define disease mechanisms and enable personalized microbiome-based approaches to prevention and treatment.