Grifola frondosa Polysaccharide F2 Ameliorates Disordered Glucose and Lipid Metabolism in Prediabetic Mice by Modulating Bile Acids

Prediabetes (pre-DM) is the buffer period before developing overt type 2 diabetes (T2DM), and the search for novel food agents to protect against pre-DM is in high demand. Our team previously reported that the <i>Grifola frondosa</i> (maitake mushroom) polysaccharide F2 reduced insulin resistance in T2DM rats induced by streptozocin (STZ) combined with a high-fat diet (HFD). This study aimed to evaluate the effects of <i>G. frondosa</i> polysaccharide F2 on disordered lipid and glucose metabolism and to investigate its mechanisms in pre-DM mice. F2 (30 and 60 mg/kg/d) was administered (i.g.) for 5 weeks to pre-DM mice. The results showed that F2 decreased the fasting blood glucose and lipid profile index of pre-DM mice (<i>p</i> < 0.05 or 0.0001). An untargeted metabolomics analysis of feces from pre-DM mice showed that F2 reduced the content of conjugated bile acids, including taurochenodeoxycholic acid and taurocholic acid, and increased the free bile acids of lithocholic acid. The results of 16S rDNA sequencing of feces from pre-DM mice showed that bile salt hydrolase (BSH)-producing bacteria, including <i>Bacillus</i>, <i>Bifidobacterium</i>, and <i>Lactococcus</i>, may be the therapy targets of F2 in pre-DM mice. Through the integrated analysis of untargeted metabolomics and 16S rDNA sequencing, it was found that F2 may ameliorate glucose and lipid metabolism disorders by promoting bile acid metabolism while regulating the abundance of BSH-producing bacteria (<i>Lactococcus</i> spp.), suggesting its potential as a functional food ingredient for the prevention of T2DM.