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Proton pump inhibitor (PPI)-containing regimens, including bismuth quadruple therapy, may perturb gut microbiota through combined exposure to acid suppression, antibiotics, bismuth, and underlying disease context. Herbal medicines and natural products have been proposed as adjunctive interventions to mitigate treatment-related microbiota perturbations; however, systematic synthesis of the clinical evidence remains limited. This systematic review and meta-analysis evaluated the effects of herbal and natural product interventions on gut microbiota and clinical outcomes in patients receiving PPI-containing therapy. Six databases (PubMed, EMBASE, Web of Science, Scopus, CENTRAL, and CNKI) were searched from their inception to March 2026. Risk of bias was assessed using RoB 2.0 and ROBINS-I. This review was prospectively registered in PROSPERO (CRD420261346672). Eighteen studies (17 randomized controlled trials, 1 observational study; n = 1984 participants) were included in the final analysis. Meta-analysis demonstrated significantly higher Helicobacter pylori eradication rates (pooled relative risk (RR) = 1.20, 95% confidence interval (CI) 1.14–1.27; I2 = 33%). Chinese-style total effective rate was also higher in the herbal groups (RR = 1.19, 95% CI 1.14–1.25; I2 = 0%), but this non-standardized outcome should be interpreted cautiously. Exploratory microbiome meta-analyses suggested higher post-treatment Bifidobacterium and Lactobacillus levels; however, substantial heterogeneity limited interpretability. Narrative synthesis revealed potential preservation of α-diversity and attenuation of pathobiont proliferation in herbal groups. Overall, herbal and natural product interventions may be associated with favorable clinical outcomes and potential microbiota-modulating effects in patients receiving PPI-containing therapy, but certainty remains limited due to methodological concerns, outcome indirectness, and heterogeneity. High-quality trials stratified by antibiotic exposure are warranted.
Hwang et al. (Tue,) studied this question.