Herbal and Natural Product Interventions to Modulate Gut Microbiota in Acid Suppression-Associated Dysbiosis: a systematic review protocol

Objectives: Proton pump inhibitors are widely used to manage acid-related gastrointestinal disorders; however, prolonged use has been associated with gut dysbiosis, including reduced microbial diversity and the proliferation of opportunistic pathogens.Herbal medicines and natural products, characterized by multitarget effects, have been proposed as potential strategies for modulating the gut microbiota and restoring microbial homeostasis.This systematic review aims to evaluate the effects of these interventions on the gut microbiota in patients receiving acid suppression therapy.Methods: This protocol is registered in the PROSPERO international prospective register of systematic reviews (CRD420261346672) and will be conducted in accordance with the PRISMA-P guidelines.A comprehensive literature search will be performed in PubMed, Scopus, Web of Science, CENTRAL, and CNKI from database inception to March 2026.Randomized controlled trials and nonrandomized controlled clinical studies evaluating herbal or natural product interventions in adult patients receiving acid suppression therapy will be included.Two independent reviewers will perform study screening, data extraction, and risk-of-bias assessment using the RoB 2 and ROBINS-I tools.The overall certainty of the evidence will be evaluated using the GRADE approach.Results: Findings will be synthesized narratively, with a focus on taxonomic shifts (from the phylum to genus level) and diversity indices (alpha and beta diversity).Where sufficient data are available, a quantitative meta-analysis will be conducted using a random-effects model.Subgroup analyses will explore differences according to herbal intervention type (e.g., single extracts vs. multiherb formulations) and microbiome assessment methods.Conclusion: This review will provide a structured overview of the microbiota-modulating effects of herbal and natural product interventions during acid suppression therapy.By bridging traditional medicine and modern microbiome science, the findings may help inform integrative therapeutic strategies and guide the design of future high-quality clinical trials.