Abstract
BACKGROUND: Distal small bowel resection with preservation of the terminal ileum (DBRPI) significantly improves glucose metabolism in rats. AIM: To explore the underlying mechanisms of DBRPI in improving glucose metabolism. METHODS: Following 8 weeks of a high-fat diet, the rats were randomly divided into the DBRPI group and the sham operation group. After surgery, body weight and glucose tolerance were monitored. At 6 weeks post-surgery, the composition of intestinal microbiota, bile acid levels, and the expression of farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5, and glucagon-like peptide-1 (GLP-1) in the ileum were examined. Additionally, the gene expression of key enzymes involved in gluconeogenesis in the liver was evaluated. RESULTS: DBRPI reduced body weight and improved glucose tolerance. At 6 weeks post-surgery, the abundance of Prevotellaceae_NK3B31_group and the level of 7-ketolithocholic acid (7-KLCA) were significantly increased, while the abundance of Desulfovibrio fairfieldensis and the level of α-muricholic acid were significantly decreased. The expression of FXR and GLP-1 in the terminal ileum was significantly upregulated. Furthermore, the expression of key gluconeogenic enzyme genes, glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1), was significantly downregulated. Correlation analysis showed that the Prevotellaceae_NK3B31_group was positively correlated with 7-KLCA and FXR, and negatively correlated with glucose tolerance, α-muricholic acid, G6PC, and PCK1. CONCLUSION: DBRPI inhibits hepatic gluconeogenesis and improves glucose metabolism. The mechanism may be related to activation of the 7-KLCA-FXR signaling pathway mediated by the Prevotellaceae_NK3B31_group.