Schizophyllum commune polysaccharide ameliorates diet-induced obesity by regulating the Faecalibaculum rodentium/indole-3-lactic acid/microRNA axis

Diet-induced metabolic disorder is a global health concern, and bioactive polysaccharides have been shown to mitigate metabolic disorder by modifying gut microbiota. Polysaccharides from Schizophyllum commune have shown excellent anti-obesity effects, but the specific regulatory mechanisms remain unclear. Herein, we reported that SCP could effectively inhibit 3 T3-L1 preadipocyte differentiation in vitro and supplementation with SCP alleviated obesity in HFD-fed mice. SCP treatment significantly enriched Faecalibaculum rodentium and ILA and increased the expression levels of several lipid metabolism-related genes including AMPKα, PGC-1α and PPARγ. The anti-obesogenic effects of SCP can be transferred by FMT. SCP supplementation and FMT significantly increased the ILA levels in serum and feces. Moreover, FMT significantly increased the levels of miR-144-5p, miR-142a-5p and miR-150-5p; these miRNAs were enriched in the phosphatidylinositol signaling pathway and were positively correlated with the content of ILA. The lipogenesis-related gene Nr2F6 was coregulated by the above miRNAs, and its expression level significantly increased in FMT mice. These results indicate that SCP ameliorates diet-induced obesity by increasing the abundance of F. rodentium and ILA as well as the expression levels of certain miRNAs. Our study may provide a new reference for understanding the anti-obesogenic effects of natural polysaccharides.