Probiotics for Irritable Bowel Syndrome: An Updated Systematic Review and Meta‐Analysis With Trial Sequential Analysis

BACKGROUND: Recent years have seen greater interest, and hence, many trials published on the topic of probiotics as a treatment for irritable bowel syndrome (IBS). Given the anticipated "multiplicity problem" and inadequacy of traditional meta-analysis, this study aims to evaluate the efficacy of probiotics in alleviating symptoms of IBS and improve quality of life through a trial sequential analysis (TSA). METHODS: Medline, Embase, Web of Science, and Cochrane were screened for randomized controlled trials (RCTs) comparing probiotics to placebo in adult patients with IBS. Primary outcomes included changes in IBS Symptom Severity Score (IBS-SSS) and IBS Quality of Life (IBS-QOL) scores. A traditional pairwise meta-analysis conducted in DerSimonian and Laird was conducted, with subsequent TSA. Study quality was graded according to risk-of-bias 2 (ROB-2), and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of 40 studies were included. Overall, probiotics demonstrated significant improvements in IBS-SSS (MD: 33.42, 95% confidence interval [CI]: -55.96 to -10.88, p < 0.01) but nonsignificant improvements in IBS-QOL (MD: 1.79, 95% CI: -3.00-6.57, p = 0.46). TSA conducted on IBS-SSS demonstrated current evidence has not reached the required information size. Cumulative Z-curve demonstrated no evidence of futility, benefit, or detrimental effect. Evaluation by ROB-2 indicates the majority of studies were of low risk of bias, while GRADE evaluation of existing evidence demonstrated low certainty of evidence, mainly attributed to inconsistency. DISCUSSION: TSA findings recommend further high-powered trials. GRADE evaluation emphasizes the importance of standardization in future trials and further efforts to identify sources of heterogeneity.