Metabolomic and Intestinal-microbial Profiling to Interpret the Mitigation of Water-soluble and insoluble Polysaccharides and Triterpenoids from <em>Poria cocos</em> against Glucolipid Metabolic Disorders

The chemical components of <em>Poria cocos</em> (PC) mainly include water-soluble polysaccharides (WSP), water-insoluble polysaccharides (WIP), and triterpenoids (TP). PC treats glucolipid metabolic disorders (GLMD), but studies on the effects and mechanisms of WSP, WIP, and TP on GLMD are lacking. GLMD rat model induced by high-fat and high-sugar diet (HFHSD) was used to evaluate the effects of TP, WSP, and WIP on GLMD. TP, WSP, and WIP were collected from PC, with purities of 88%, 90%, and 91%, respectively. They decreased lipid levels in serum and liver, reduced hepatic steatosis and blood sugar, improved insulin resistance, as well as gastrointestinal and liver mitochondrial function. Differential metabolites involved in the regulation of metabolic pathways were restored to the normal values by TP, WSP, and WIP. TP and WIP regulated EPT1, LCAT, and LPCAT2 levels in the glycerophospholipid metabolism pathway, while WSP regulated EPT1 and LCAT levels in the glycerophospholipid metabolism pathway. TP and WIP regulated sPLA2 level in the arachidonic acid metabolism pathway. TP, WSP, and WIP regulated ALDH7A1 level in the lysine degradation pathway. TP, WSP, and WIP regulated the diversity, richness, and community structure of gut microbiome at the phylum, genus, and species levels associated with the pharmacological indicators total cholesterol (TC), triglyceride (TG), and acetyl choline (ACH), as well as several metabolic pathways. Therefore, TP, WSP, and WIP alleviated GLMD by ameliorating gastrointestinal and liver mitochondrial function, mainly involved in the regulation of lipid, amino acid, cofactors, and vitamins, and gut microbiome. They constitute the main material basis for PC's efficacy against GLMD.