Abstract
BACKGROUND: The management of small intestinal bacterial overgrowth (SIBO) involves a range of therapeutic options such as antibiotics, probiotics, and prokinetic agents, yet their comparative clinical efficacy remains poorly characterized. OBJECTIVE: To address this critical evidence gap, we systematically evaluated all empirically used treatment regimens through a network meta-analysis (NMA) of published randomized controlled trials (RCTs), with the goal of providing clearer guidance for therapeutic selection. DESIGN: We conducted a systematic review and NMA following established methodological standards for evidence synthesis. DATA SOURCES AND METHODS: Our comprehensive literature search covered PubMed/MEDLINE, Embase, and Web of Science from their inception through December 31, 2024. We included RCTs examining SIBO treatments in adult populations. The extracted data from qualifying RCTs were subjected to Bayesian NMA to (1) conduct pairwise comparisons of empirical SIBO treatment regimens and (2) determine their hierarchical efficacy ranking. The ranking probability for each regimen was evaluated by means of the surfaces under cumulative ranking values. RESULTS: Our NMA incorporated 30 eligible RCTs, involving a total of 1552 participants and evaluating 12 distinct interventions. Based on comparative efficacy rankings, berberine was associated with the highest surface under the cumulative ranking curve (SUCRA) value, positioning it as a potentially favorable option for SIBO eradication. In the subgroup of patients with concurrent functional gastrointestinal disorders (FGIDs), the combination of rifaximin and a gastrointestinal motility drug also showed a high SUCRA value (89%), suggesting it may represent a particularly effective regimen in this clinical context. Furthermore, among SIBO patients with chronic liver disease, the gastrointestinal motility drug alone exhibited the most favorable ranking trend (SUCRA: 79.6%). While three of the included studies were assessed as having a high risk of bias (RoB), meta-regression analysis indicated that the RoB did not significantly influence the model outcomes. The confidence in network estimates was generally rated as high across the treatment comparisons. CONCLUSION: This NMA suggests that the management of SIBO may be optimized by considering specific patient comorbidities. Three principal clinical scenarios were identified: First, for patients with uncomplicated SIBO, berberine monotherapy displayed the highest ranking in terms of comparative efficacy. Second, in those with concomitant FGIDs, a combination of rifaximin and a prokinetic agent appeared to be the most promising approach. Finally, among individuals with SIBO and chronic liver disease, prokinetic therapy alone was ranked as the most favorable intervention. These findings highlight the potential for tailored treatment strategies; however, given the methodological heterogeneity and limited sample sizes in some subgroups, the results should be interpreted as generating hypotheses for future validation in well-controlled, direct-comparison studies. TRIAL REGISTRATION: This NMA was registered with PROSPERO (Registration ID: CRD420251075028).