Comparative efficacy and tolerability of probiotic, prebiotic, and synbiotic formulations for adult patients with mild-moderate ulcerative colitis in an adjunctive therapy: A network meta-analysis

Probiotics, prebiotics, and synbiotics (PPS) have been widely used as adjuvant treatments in patients with ulcerative colitis (UC) in recent years. However, the most effective formulations of PPS have yet to be identified. We thus aimed to compare the efficacy and tolerability of different PPS formulations for mild-moderate UC.We searched PubMed, Embase, Web of Science, and Cochrane CENTRAL from inception to June 24, 2023 for double-blind randomized controlled trials. We used a frequentist approach in random-effects models for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of evidence.We analysed data from 20 trials involving 1153 patients. The combinations of specific strains of Lactobacillus and Bifidobacterium (CLB) (odds ratio (OR), 3.85; 95 % confidence interval (CI), 1.40-10.60; low certainty) and combinations of specific strains of Lactobacillus, Bifidobacterium, and Streptococcus (CLBS) (OR, 2.20; 95 % CI, 1.47-3.28; low certainty) significantly increased the clinical remission rate in intention-to-treat analysis (ITT) when compared to placebo. Similarly, compared with placebo, the two combinations significantly reduced clinical activity scores (standardized mean difference (SMD), -1.17 (95 % CI, -1.68 to -0.65), low certainty; and SMD, -1.33 (95 % CI, -1.81 to -0.86), low certainty, respectively). Hierarchical cluster analyses showed the two combinations formed clusters with high efficacy (clinical remission in ITT and clinical activity score) and tolerability (withdrawal due to worsening symptoms) within 12 weeks.In this systematic review, we found CLB and CLBS demonstrated a clinical benefit in adjuvant treatments, with a comparable tolerability and safety profile to placebo. Further trials are needed.CRD42022344905.