Polygonatum sibiricum saponin-lactic acid bacteria combination attenuate hyperglycemia in T2DM mice by modulating amino acid metabolism

Some research have shown that the combination of plant extracts and probiotics may be a better way to treat type 2 diabetes mellitus (T2DM) than a single intervention. However, there are still relatively few relevant reports in this aspect. Therefore, this study aims to investigate whether the treatment of Polygonatum sibiricum saponin (PSS) and lactic acid bacteria (LAB) combination can better manage T2DM. And the anti-diabetes mechanism of the combination was studied from the perspectives of glucose metabolism, microbiome and metabolome. The results showed that PSS + LAB could better improve fasting blood glucose level, insulin sensitivity, lipid metabolism disorder, and liver function. Protein analysis showed that PSS + LAB treatment significantly increased the expression of phosphorylated-phosphatidylinositol 3 kinase (p-PI3K)/PI3K, phosphorylated-protein kinase B (p-AKT)/AKT, glucose transporter 2 (GLUT2), insulin receptor substrate 2 (IRS2), and glycogen synthase kinase 3(3 (GSK-3(3) in the liver of T2DM mice, while inhibiting the expression of forkhead box protein O1 (FoxO1). This combination positively regulated the composition and abundance of the gut microbiota. Metabolomic analysis showed that the combination treatment exhibited more changes in gut microbiota metabolites compared to PSS treatment alone. The alteration of gut microbiota by LAB + PSS led to significant changes in alanine, aspartate and glucose metabolism pathways. This study may provide a theoretical basis for the combined application of plant extracts and probiotics for the management of T2DM. (c) 2025 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).