Galactooligosaccharide-Metabolism-Related Genes of Bifidobacterium pseudocatenulatum Contribute to the Regulation of Glucose and Lipid Metabolism in Type 2 Diabetic Mice

This study investigated whether the galactooligosaccharide (GOS)-metabolism-related genes (GOS-cluster) in Bifidobacterium pseudocatenulatum contribute to alleviating glucose and lipid metabolic disorders in type 2 diabetic mice. Genomic analysis of 69 B. pseudocatenulatum strains based on the GOS-cluster, combined with in vitro fermentation experiments, revealed that high-GOS-cluster strains (≥24 MFS, ≥39 GOS-cluster) demonstrated superior GOS utilization and bile salt tolerance. In vivo, the high-GOS-cluster strains resulted in a significant reduction of blood glucose levels by 18.52 to 32.01% compared to the model group. Mechanistic studies showed that these strains significantly activated the FXR/FGF15/GSK3β and FXR/SREBP1/FAS signaling pathways. Species-specific quantification of B. pseudocatenulatum, metabolomics, and network analysis suggested that GOS treatment increased the abundance of B. pseudocatenulatum, particularly strains rich in the GOS-cluster, with a 32.03% increase compared to strains with a low GOS-cluster. This indirectly increased choloylglycine hydrolase levels and altered the profiles of primary and secondary bile acids, resulting in an increase in FXR agonists, such as glycocholic acid, cholic acid, and deoxycholic acid. These findings suggest that the presence of the GOS-cluster is a crucial factor in determining whether a B. pseudocatenulatum strain can prevent or ameliorate type 2 diabetes.