Antibiotics are very effective in treating a variety of bacterial infections, while clinical overuse of antibiotics can lead to diseases such as antibiotic-associated diarrhea. Numerous studies have shown that natural polysaccharides can be used as prebiotics to alleviate antibiotic-associated diarrhea (AAD). Poria cocos is a medicinal and edible mushroom widely used for thousands of years in China, and our former study demonstrated that water-insoluble polysaccharide (PCY) has the potential prebiotic function. Therefore, we simulated the digestion and fermentation of PCY using feces from volunteers, and then administered it to C57BL/6 mice with AAD to study its effects on the gut microbiota and metabolites. The results indicated that PCY effectively alleviated the symptoms of AAD in mice, restored the intestinal barrier function, improved the content of short-chain fatty acids (SCFAs), decreased the level of inflammatory cytokines, and changed the structure of gut microbiota by increasing the relative abundance of norank_f__Muribaculaceae and unclassified_f__Lachnospiraceae, and decreasing that of Escherichia-Shigella, Staphylococcus and Acinetobacter. This study further demonstrated that PCY is an effective functional prebiotic for improving AAD disease, and provided a new avenue and insight for developing PCY as a functional food or prebiotic for alleviating gastrointestinal diseases.

Wolfiporia cocos (F. A. Wolf) Ryvarden and Gilb. is a widely used herb in China, belonging to the large fungi of the family Polyporaceae. P. cocos; it consists of a variety of biologically active ingredients such as polysaccharides, triterpenes, and sterols, and is considered a treasure in traditional Chinese medicine (TCM). Notably, P. cocos polysaccharides, as the most prominent constituent, are of interest for their superior anti-obesity, anti-tumor, anti-inflammatory, antioxidant, and immunomodulatory activities. P. cocos polysaccharides can be divided into water-soluble polysaccharides and water-insoluble polysaccharides, which may contribute to their diverse biological functions. Numerous scholars have focused on the extraction process, structural identification, and classical pharmacological pathways of P. cocos polysaccharides, but there are few systematic reviews on P. cocos polysaccharides regulating the gut microbiota. Natural products and their active ingredients are closely related to intestinal health, and further exploration of these mechanisms is warranted. This review summarizes the recent cases of P. cocos polysaccharides regulating the gut microbiota to promote health and discusses their relationship with bioactive functions. It aims to provide a basis for exploring the new mechanisms of P. cocos polysaccharides in promoting intestinal health and offers a new vision for the further development of functional products.

Conventional prebiotics lack the structural specificity to direct colonic fermentation toward defined outputs. Dietary polysaccharides (DPs) serve as direct fermentation substrates, and their architecture—monosaccharide composition, glycosidic linkages, molecular weight and branching—determines which short-chain fatty acid (SCFA)-producing taxa can access them. This selectivity is governed by carbohydrate-active enzyme (CAZyme) repertoires and cross-feeding networks. We propose a dual-track precision framework: structure-guided matching of DPs to target SCFA producers, and individualized selection informed by baseline microbiota and disease-specific deficits. The proposed dual-track framework is a theoretical model that requires rigorous validation in human clinical trials. This work provides a mechanism-driven theoretical basis for advancing dietary polysaccharides from empirical prebiotics to precision nutrition tools.

Background: Metabolic diseases—including obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD)—affect over 1 billion individuals globally and are characterized by insulin resistance, chronic inflammation, and gut microbiota dysbiosis. Herbal medicines offer multi-component therapeutic potential through microbiota modulation, but mechanistic insights remain fragmented. Objective: This review synthesizes recent advances in herbal medicine-mediated gut microbiota regulation in metabolic diseases and delineates underlying molecular mechanisms. Methods: A comprehensive literature search was conducted across PubMed and Web of Science. Search strategies employed MeSH terms and free-text keywords encompassing herbal medicines, gut microbiota, and metabolic diseases. Two authors performed study selection and data extraction. Evidence synthesis was structured according to intervention type and metabolic disease category. Results: Herbal polysaccharides and other compounds consistently increased beneficial bacteria and promoted short-chain fatty acids (SCFAs) production, improving intestinal barrier integrity via ZO-1/Occludin upregulation and attenuating TLR4/NF-κB-mediated inflammation. Herbal formulations exerted synergistic effects by remodeling microbial community structure, correcting SCFA/bile acid imbalances, and activating IRS1/PI3K/AKT insulin signaling. Notably, Lactobacillus and Akkermansia emerged as recurrent beneficial targets across multiple herbal interventions. However, evidence is predominantly preclinical, and translational validity to humans requires further validation. Conclusion: Herbal medicines ameliorate metabolic diseases through multi-target gut microbiota modulation, involving SCFA production, bile acid metabolism, and inflammatory pathway attenuation. These mechanistic insights support the development of microbiota-targeted herbal therapeutics, though clinical translation necessitates standardized formulations and rigorous human trials.