Multi-omics analysis reveals the anti-obesity and hepatoprotective properties in Termitomyces intermedius extracts

Termitomyces species are edible mushrooms that have been documented to possess beneficial medicinal properties. Termitomyces intermedius is a recently identified species that has not yet been fully investigated for its potential effects on obesity. This study aimed to evaluate the anti-obesity effects of Termitomyces intermedius methanolic extracts (TIE) in C57BL/6J mice subjected to a high-fat diet (HFD). Over a 12-week period, the mice were treated with TIE at daily doses of 75 and 150 mg/kg. A comprehensive analysis of obesity-related indicators, serum metabolomics, gut microbiota composition, and flavonoid profiling was conducted. Our results indicated that high dosage of TIE intervention significantly prevented weight gain by nearly 60% when compared to control group, along with improved glucose homeostasis, lowered circulating triglycerides, cholesterols, low-density lipoprotein-cholesterols, alanine aminotransferase, aspartate aminotransferase levels and increased high-density lipoprotein cholesterols. TIE supplementation reduced hypertrophy of hepatocytes and epididymal adipocytes. Metabolomic analysis identified 2,788 metabolites in total and TIE enriched 30 of them, including 7 metabolic pathways associated with lipid and amino acid metabolism. Furthermore, the intervention was associated with an enrichment of beneficial bacterial taxa including Muribaculaceae, Blautia and a reduction in potentially harmful microbes including Alistipes and Bacteroides , suggesting a positive modulation of the gut microbiome. Flavonoid profiling revealed the rich abundance of apigenin, luteolin and quercetin which are believed to contribute to its anti-obesity properties. As the first study to investigate the pharmaceutical properties of Termitomyces intermedius , this work underscores the multifaceted anti-obesity pathways of TIE, including the synergistic impact of its flavonoid constituents. These findings provide a robust theoretical basis for further exploration of TIE's therapeutic potential in personalized nutrition and dietary interventions for obesity management.