A meta-analysis of berberine combined with brain-gut axis-targeted agents for diarrhoea-predominant irritable bowel syndrome

Abstract

The prevalence of diarrhoea-predominant irritable bowel syndrome (IBS-D) is high and significantly impairs patient quality of life. Berberine, a naturally occurring isoquinoline alkaloid, shows promise in combination with brain-gut axis-targeted drugs for relieving abdominal pain, bloating, and diarrhoea in IBS-D. However, current clinical evidence remains insufficient to conclusively substantiate its efficacy. Through a systematic literature review and meta-analysis, this work comprehensively evaluated the efficacy and safety of berberine in combination with brain-gut axis-targeted medications for the treatment of IBS-D, thereby providing evidence to inform clinical practice. On 1 December 2025, a comprehensive search was conducted across ten databases, including PubMed, Web of Science (WOS), the Cochrane Library, and Embase, to identify randomized controlled trials (RCTs) evaluating berberine in combination with brain-gut axis-targeted medications. Two reviewers independently screened the literature according to predefined inclusion and exclusion criteria, followed by data extraction. The risk of bias tool developed by the Cochrane Collaboration was used to assess the methodological quality of the included studies, and data were analyzed using RStudio software. When two or more studies had comparable interventions and outcome measures, a meta-analysis was conducted, otherwise, a qualitative synthesis was performed. The certainty of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A total of 19 RCTs involving 1,489 participants were included in the analysis. Compared with the control groups, the intervention groups showed significant improvements in IBS-D symptoms and patient quality of life. Specifically, combination therapy incorporating berberine significantly increased the overall treatment response rate (odds ratio = 4.19, 95% confidence intervals (CI): 3.13–5.61). With respect to continuous outcomes, combination therapy significantly reduced overall symptom scores (standardized mean difference (SMD) = −3.47, 95% CI: −6.65 to −0.29), particularly reflected by reductions in abdominal pain and bloating severity, along with improvements in diarrhoea-related symptoms. Furthermore, no serious adverse events were reported across the included trials. Berberine combined with brain-gut axis-targeted medications shows promising efficacy and acceptable safety in the treatment of IBS-D. However, existing studies are limited by small sample sizes and methodological weaknesses, and the overall strength of evidence remains insufficient. Larger, rigorously designed RCTs are needed to further confirm its efficacy and safety. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251238184 , identifier CRD420251238184.