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

ABSTRACT 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.