Safety and efficacy of microbiota-directed adjunctive therapy in acute pancreatitis: a systematic review and meta-analysis of prebiotics, probiotics, and synbiotics.

BACKGROUND: Prebiotics, probiotics, and synbiotics have been proposed as adjunctive treatments for acute pancreatitis (AP), but their clinical efficacy and safety remain uncertain. We conducted a systematic review and meta-analysis to evaluate their effects on recovery-related, efficacy, and safety-critical outcomes in AP. METHODS: PubMed, Web of Science, Scopus, Embase, and the Cochrane Library were searched through July 2026, supplemented by Google Scholar and reference-list screening. Comparative interventional and observational studies evaluating prebiotics, probiotics, or synbiotics versus placebo, standard care, or nutritional controls were eligible. Risk of bias was assessed using Cochrane RoB 2 for randomized studies and the Newcastle-Ottawa Scale for non-randomized studies. Random-effects meta-analyses were performed using mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Sensitivity and subgroup analyses were conducted to explore study quality and clinical heterogeneity. RESULTS: 30 studies were included in the systematic review and 25 in the meta-analysis. Microbiota-directed interventions were associated with a shorter hospital stay in the full-analysis set (MD - 4.68 days, 95% CI - 6.22 to -3.14), although heterogeneity was substantial (I2 = 98.74%); the association persisted in the sensitivity analysis (MD - 3.90 days, 95% CI - 5.93 to -1.87). Mortality was lower in the full analysis (RR 0.67, 95% CI 0.45-0.98), but this finding was not robust and lost statistical significance in the sensitivity analysis. Total infection (RR 0.50, 95% CI 0.36-0.69) and infectious morbidity (RR 0.58, 95% CI 0.42-0.80) were reduced, whereas infected pancreatic necrosis, organ failure/multiple organ failure, need for operation, and systemic inflammatory response syndrome were not significantly improved overall. Adverse-event reporting was inconsistent, and a large multicenter trial provided an important safety signal for live multispecies probiotics in predicted severe AP. CONCLUSION: Microbiota-directed interventions may be associated with shorter hospital stay and fewer infection-related complications, but substantial heterogeneity, intervention diversity, and incomplete safety reporting limit clinical interpretation. Evidence for mortality or other severe outcomes is not robust. Current evidence does not support routine use of these interventions in AP, particularly live probiotic preparations in severe or critically ill patients. Future adequately powered, severity-stratified trials using standardized formulations and prospective safety monitoring are needed. SYSTEMATIC REVIEW REGISTRATION: Registration number: CRD420261387279.