Distal small bowel resection with the preservation of terminal ileum suppresses hepatic gluconeogenesis via the Prevotellaceae_NK3B31_group-mediated 7-KLCA-FXR axis

Previous studies have indicated that distal small bowel resection with preservation of the terminal ileum (DBRPI) significantly lowers blood glucose levels and improves glucose tolerance, presumably through mechanisms involving increased bile acid levels and increased glucagon-like peptide-1 secretion. In this study, we observed time-dependent increases in glucose tolerance and weight loss following DBRPI, accompanied by certain beneficial alterations in lipid metabolism. At 6 weeks postsurgery, we noted a significant downregulation of the key gluconeogenic enzyme-encoding genes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in addition to the upregulation of farnesoid X receptor and glucagon-like peptide-1 in the terminal ileum. Additionally, DBRPI increased the abundance of Prevotellaceae_NK3B31_group and elevated 7-ketolithocholic acid (7-KLCA) levels while reducing the abundance of Desulfovibrio_fairfieldensis and α-muricholic acid levels. Further correlation analysis revealed a significant positive association between the increased abundance of Prevotellaceae_NK3B31_group and altered glucose metabolism indicators. Our findings suggest that DBRPI can increase glucose metabolism in obese rats by inhibiting hepatic gluconeogenesis, potentially through the activation of the Prevotellaceae_NK3B31_group -induced 7-KLCA-FXR signaling pathway.