Chayote pectin regulates blood glucose through the gut-liver axis: Gut microbes/SCFAs/FoxO1 signaling pathways

Despite significant evidence on the anti-diabetic effect of chayote fruit and phenolic compounds, research on the mechanism of chayote ( Sechium edule) pectin (CP) regulating blood glucose in type 2 diabetes mellitus (T2DM) is scarce. Therefore, this study aims to explore the potential mechanisms by which CP modulates blood glucose levels through an 8-week administration in db/db mice. The results showed that the CP treatment in db/db mice resulted in an elevation in glucagon-like peptide (GLP-1) secretion, an increase in hepatic glycogen storage, and a decrease in homeostasis model assessment-insulin resistance (HOMA-IR). Western blotting results showed that CP intervention significantly upregulated the expression of phosphatidylinositol 3 kinase (PI3K), phosphorylated protein kinase B (P-AKT) and downregulated the expression of fork-head transcription factor O1(FoxO1), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Moreover, CP effectively upregulated the protein expression of hepatic G protein-coupled receptor 43 (GPR43) and phosphorylated adenosine 5 '-monophosphate (AMP)-activated protein kinase (P-AMPK). Furthermore, CP rearranged the gut microbiota structure by increasing beneficial bacteria ( unclassified_Ruminococcaceae , Muribaculaceae, Alloprevotella, Rikenella, and Parabacteroides) and reducing the Firmicutes/Bacteroidetes ratio. Additionally, CP improved the gut barrier by increasing the number and area of goblet cells and significantly upregulating the expression of Claudin-1 and Mucin-2. Overall, these findings suggest that CP regulated blood glucose by activating the gut- liver axis signaling pathway: gut microbiota/ SCFAs/ GLP-1, PI3K/AKT/FoxO1, and GPR43/AMPK/FoxO1. This study provides a scientific basis for the development and application of pectin-based functional foods.