An integrated fecal microbiome and metabolomics in type 2 diabetes mellitus rats reveal mechanism of action of Moringa oleifera Lamarck seeds polysaccharides to alleviate diabetes

Moringa oleifera Lamarck seeds (MOS) have been traditionally used in folk medicine and documented for their potential to alleviate type 2 diabetes symptoms, but the potential mechanisms are still unknown. The purpose of this article is to investigate the effects of MSAP (alkali-extracted polysaccharide from MOS) on diabetic rats by assessing its impact on the gut microbiome, diabetes-related biochemical markers, and fecal metabolomics. The results demonstrated that the fasting blood glucose, glucose tolerance, insulin resistance, insulin level and lipopolysaccharides (LPS) level in the rats treated with MSAP were all improved. Specifically, MSAP was found to modulate the composition and diversity of the gut microbiota, increasing the ratio of Firmicutes/Bacteroidetes, which enhanced the quantity of probiotic Lactobacillus and butyrate-producing bacteria, such as Roseburia, thereby reinforcing the intestinal epithelial barrier. Furthermore, fecal metabolomics indicates that MSAP actively regulates pathways closely associated with diabetes, including sphingolipid metabolism, amino acid synthesis and catabolism, retrograde endogenous cannabinoid signaling, and the modulation of TRP channels by inflammatory mediators. By integrating microbiome and metabolomics data, this study elucidated the mechanisms through which MSAP alleviates diabetes. In conclusion, the findings suggest that polysaccharides from MOS hold potential as a medicinal and edible homologous food for diabetes management.