Probiotic or synbiotic interventions and chemotherapy-associated diarrhea in cancer patients: a meta-analysis of randomized trials

• First systematic evaluation of differentiated efficacy in CAD of varying severities • The study systematically evaluates the differentiated efficacy of probiotics/synbiotics in chemotherapy-associated diarrhea (CAD) across different severity levels for the first time, breaking through traditional single-efficacy evaluation models. It also extends the analysis to assess their impacts on multiple types of chemotherapy-related adverse reactions, including constipation, nausea, stomatitis, neutropenia, and thrombocytopenia, thereby expanding the evaluation dimensions for the application of probiotics in oncological supportive care. • Innovative revelation of ethnic and geographical heterogeneity in efficacy • This study innovatively reveals the ethnic and geographical differences in the efficacy of probiotics/synbiotics (Asian vs. European & American populations). By integrating subgroup analyses (e.g., geographical regions, strain types, dosage) and sensitivity analyses, it validates the robustness of efficacy heterogeneity, providing cross-ethnic evidence-based references for clinical precision medicine and filling research gaps in the mechanisms of probiotics across different populations. • Enhanced reliability through stratified analysis and sensitivity testing • The study strengthens the reliability of its conclusions through stratified analyses of mild and severe diarrhea, as well as multi-factor sensitivity analyses, in line with rigorous methodological standards emphasized in the checklist (e.g., systematic review registration and data integrity requirements). The incidence of chemotherapy-associated diarrhea (CAD) ranges from 50% to 80%, which significantly impairs the treatment efficacy and the quality of life of cancer patients. Existing interventions are associated with side effects, and probiotics or synbiotics may represent a new approach, yet the evidence regarding their efficacy remains controversial. This study aimed to quantify the effect of probiotics/synbiotics in alleviating CAD via meta-analysis and to explore factors that might influence their effectiveness. Following the PRISMA framework, we searched databases including CENTRAL and MEDLINE for randomized controlled trials (RCTs) up to October 2025, enrolling cancer patients who received chemotherapy alone. Using software such as RevMan and Stata, the relative risk (RR) was adopted as the effect measure. Heterogeneity was assessed via the Q-test and I 2 statistic, and the quality of evidence was evaluated using the GRADE approach. A total of 15 RCTs involving 1,488 patients were included. Probiotics or synbiotics significantly reduced overall incidence of CAD in adults (RR=0.63, 95% CI [0.50, 0.80], p =0.0002), with a more pronounced effect on severe CAD (RR=0.30, p =0.02); however, the evidence for mild CAD was insufficient, primarily due to an inadequate sample size. Populations in East and Southeast Asia derived greater benefits (RR=0.51, p =0.02). Probiotics or synbiotics also significantly reduced the incidence of constipation (RR=0.56, p =0.01) but showed no consistent effects on other adverse reactions such as nausea. The GRADE quality of evidence was rated as "very low".