Herbal and Natural Product Interventions in Animal Models of Antibiotic-Associated Diarrhea and Their Effects on Gut Microbiota: a protocol for systematic review

Objectives: Antibiotic-associated diarrhea (AAD) is a frequent complication of antibiotic use and is commonly used to investigate gut microbiota dysbiosis and potential therapeutic interventions in animals. Herbal medicines and natural product-derived compounds have shown promising effects in restoring microbial balance; however, no systematic review has yet synthesized the preclinical evidence. Therefore, this review aimed to systematically identify, evaluate, and synthesize animal studies examining herbal and natural product interventions for AAD, with a particular focus on gut microbiota restoration and related functional outcomes. Methods: This protocol has been registered in PROSPERO (CRD420251136553). A systematic search was performed in PubMed, Embase, Web of Science, Scopus, CNKI, and other major Korean medical databases from inception to the search date. Controlled preclinical studies that evaluated herbal or natural product interventions for AAD in animal models and reported gut microbiota outcomes were also included. Two reviewers independently screened the studies, extracted the data, and assessed the risk of bias. Results: This systematic review was conducted in accordance with the PRISMA guidelines. The findings were synthesized narratively and, where appropriate, organized by intervention type, animal model, and microbiome analytic method. Conclusion: This review systematically evaluates the effects of herbal and natural products on the gut microbiota in animal models of antibiotic-associated diarrhea. These findings provide foundational preclinical evidence to support microbiome-directed development of herbal, polysaccharide-based, and synbiotic interventions for antibiotic-associated dysbiosis.