<em>Spirulina platensis</em> polysaccharide and its selenide ameliorate lipid metabolism disorders and gut microbiota dysbiosis in type 2 diabetic mice

Type 2 diabetes mellitus (T2DM) is a chronic endocrine disorder characterized by metabolic disturbances. Currently, the treatment strategies for T2DM mainly focus on improving insulin sensitivity and regulating blood glucose homeostasis. However, due to the incomplete understanding of the interaction network mediating gene-metabolism-microbiota regulation, breakthroughs in targeted therapy have been limited. In this study, the hypoglycemic effects of<em> Spirulina platensis</em> polysaccharide (SPP) and its selenium-modified polysaccharide (SeSPP) on a high-fat diet/streptozotocin-induced T2DM mice model were thoroughly investigated, along with their underlying mechanisms. Transcriptomics and metabolomics analysis revealed that SPP and SeSPP exerted their hypoglycemic effects primarily by regulating lipid metabolism, carbohydrate metabolism, and cellular signaling pathways. They resulted in a reduction of Propionyl-CoA and Lyso-PI (0:0/18:1(9Z)) levels, while simultaneously increasing the level of 12,13-diHOME. Furthermore, they upregulated the expression of the <em>Acot3</em> gene and downregulated the expression of the <em>Acsm2</em> gene, thereby activating the fatty acid metabolic pathway. SPP and SeSPP significantly ameliorated the gut microbiota imbalance induced by T2DM by enhancing the abundance of<em> Lactobacillus</em> and <em>Faecalibaculum</em>, while simultaneously reducing the levels of <em>Alloprevotella</em> and <em>Bacteroides</em>. In conclusion, SPP and SeSPP have the potential to reshape the gut microbiota, thereby restoring microecological balance, including disorders in glucose and lipid metabolism, chronic low-grade inflammation, and oxidative stress.