Heptamethoxyflavone Alleviates Metabolic Syndrome in High-Fat Diet-Fed Mice by Regulating the Composition, Function, and Metabolism of Gut Microbiota

3,5,6,7,8,3 & PRIME;,4 & PRIME;-Heptamethoxyflavone (HMF)could prevent obesity and hyperlipidemia,but its effects on gut microbiota andfecal metabolites remain unclear. Here, the effect of HMF on metabolicsyndrome (MS) was evaluated in high-fat diet (HFD)-fed mice, and itsunderlying mechanisms were revealed by integrative metagenomic andmetabolomic analyses. We demonstrated that HMF could effectively ameliorateHFD-induced MS by alleviating body-weight gain, fat accumulation,hepatic steatosis, and lipid and glucose abnormalities. HMF significantlyaltered the gut microbiota composition in HFD-fed mice with enrichmentof short-chain fatty acid (SCFA)- and bile acid-producing beneficialbacteria and inhibition of harmful bacteria. Also, HMF improved microbialfunctions by up-regulating bile acid metabolism and down-regulatingfatty acid metabolism and inflammatory response-related pathways.Consistent with the gut microbial changes, HMF altered the fecal metaboliteprofile of HFD-fed mice, mainly characterized by increasing SCFA andseveral bile acid levels as well as lowering several lysophospholipidsand fatty acid levels. Correlation analysis indicated that three keyspecies Faecalibaculum rodentium, Collinsella aerofaciens, and Lactobacillusfermentum and the increase in microbial metabolites,i.e., SCFAs and secondary bile acids, might play a positive role inalleviating MS. Our results suggested that HMF alleviated HFD-inducedMS possibly by modulating the composition, function, and metabolismof gut microbiota.