Cyclocarya paliurus Polysaccharides Attenuate High‐Fat Diet‐Induced Metabolic Dysfunction via Gut Microbiota Remodeling

BACKGROUND AND AIM: Alterations in gut microbiota composition are closely associated with obesity and metabolic disorders. Cyclocarya paliurus polysaccharides (CCPP) have been shown to improve lipid metabolism and modulate the gut microbiota; however, mechanistic evidence remains limited and may vary depending on preparation methods. This study investigated whether a crude polysaccharide-enriched Cyclocarya paliurus preparation alleviates high-fat diet-induced metabolic dysfunction and is associated with gut microbiota remodeling. METHODS: Male C57BL/6 J mice were randomized into three groups: normal diet (ND), high-fat diet (HFD), and HFD supplemented with CCPP for 12 weeks. Serum metabolic parameters were measured; intestinal inflammatory cytokine transcripts were assessed by qRT-PCR; and cecal microbiota composition was analyzed by 16S rRNA gene sequencing. Additionally, fecal microbiota transplantation (FMT) was performed by transferring microbiota from CCPP-treated donors to antibiotic-pretreated HFD-induced recipients for 8 weeks. RESULTS: CCPP attenuated HFD-induced body weight gain and reduced subcutaneous and visceral adipose tissue mass. CCPP significantly improved serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) and reduced fasting glucose. Cecal 16S rRNA gene profiling showed that CCPP reshaped the gut dysbiosis associated with a HFD and enriched microbial taxa that are commonly linked to carbohydrate fermentation. These taxa specifically include Lachnospiraceae-related microbial taxa and Ileibacterium. Importantly, FMT from CCPP-treated donors recapitulated these metabolic improvements, confirming that the benefits of CCPP were microbiota-dependent. CONCLUSION: CCPP mitigates obesity and metabolic dysfunction by remodeling the gut microbiota, particularly by enriching short-chain fatty acid-producing taxa. These findings highlight CCPP as a potential microbiota-targeted therapeutic agent for metabolic disorders.