Total proctocolectomy with ileal J-pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with refractory ulcerative colitis (UC). Although the surgery generally cures UC allowing a significant improvement of health-related quality of life, complications can occur after IPAA. The most common complication of this surgery is pouchitis, a non-specific inflammatory condition at the ileal pouch reservoir occurring in up to 50% of patients, with 10%% of these patients becoming chronic sufferers. Although the etiology and pathogenesis of pouchitis are still not entirely clear, the bulk of the evidence points towards an abnormal mucosal immune response to altered microbiota patterns. The management of pouchitis is largely empirical and only a few small placebo-controlled clinical trials have been conducted. Although antibiotics represent the mainstay of treatment, probiotics have recently gained more attention as an effective therapeutic option for pouchitis management. However, little is known about the molecular mechanisms underlying the protective effects of probiotics against pouchitis onset.