Rifaximin Versus Placebo for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Rifaximin, a minimally absorbed broad-spectrum oral antibiotic, is used to target gut dysbiosis in patients with irritable bowel syndrome (IBS).However, conflicting trial data and methodological heterogeneity necessitate an updated, rigorous synthesis of its efficacy and safety profile.We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing rifaximin with placebo in adult patients with IBS, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines.The primary outcome was global symptom relief at the end of the treatment.Data were pooled using inverse-variance random-effects models with Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment.Evidence robustness was evaluated using prediction intervals (PI), Trial Sequential Analysis (TSA), trim-and-fill algorithms for publication bias, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Nine RCTs (yielding 10 randomized comparisons due to one trial's a priori stratification by small intestinal bacterial overgrowth status) were included in this review.For the primary outcome (eight comparisons, N=2,056), rifaximin significantly improved global symptom relief compared to placebo (RR 1.54, 95% CI 1.13 to 2.11; p=0.014), corresponding to a number needed to treat for benefit (NNTB) of 6.However, statistical heterogeneity was substantial (I 2 =59.5%), and the 95% PI crossed the line of no effect (0.89-2.67).The primary effect lost statistical significance upon the exclusion of high-risk-of-bias trials (RR 1.47, 95% CI 0.95-2.27)and after adjusting for publication bias using the trim-and-fill method (RR 1.37, 95% CI 0.93-2.01).The TSA indicated that the accrued information size remained inconclusive for a conservative 15% relative benefit.Rifaximin demonstrated no statistically detectable difference in adverse events compared to placebo, though this is accompanied by considerable uncertainty (Peto OR 0.89 (95% CI 0.65-1.22)).Rifaximin demonstrates a modest overall benefit for global IBS symptoms and an excellent safety profile; however, the certainty of evidence is very low.The apparent efficacy is highly fragile, driven largely by industry-funded trials, undermined by publication bias, and characterized by wide prediction intervals.Biomarker-guided stratification, such as testing for small intestinal bacterial overgrowth (SIBO), may be required to optimize patient selection in future independent trials.