Sargassum fusiforme Alginate Relieves Hyperglycemia and Modulates Intestinal Microbiota and Metabolites in Type 2 Diabetic Mice

Sargassum fusiforme alginate (SF-Alg) possess many pharmacological activities, including hypoglycemic and hypolipidemic. However, the hypoglycemic mechanisms of SF-Alg remain unclear due to its low bioavailability. In this study, we evaluated the therapeutic effect of SF-Alg on high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2D) mice. SF-Alg intervention was found to significantly reduce fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC), while increasing high-density lipoprotein cholesterol (HDL-c) and improving glucose tolerance. In addition, administrating SF-Alg to diabetic mice moderately attenuated pathological changes in adipose, hepatic, and heart tissues as well as skeletal muscle, and diminished oxidative stress. To probe the underlying mechanisms, we further analyzed the gut microbiota using 16S rRNA amplicon sequencing, as well as metabolites by non-targeted metabolomics. Here, SF-Alg significantly increased some benign bacteria (Lactobacillus, Bacteroides, Akkermansia Alloprevotella, Weissella and Enterorhabdus), and significantly decreased harmful bacteria (Turicibacter and Helicobacter). Meanwhile, SF-Alg dramatically decreased branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the colon of T2D mice, suggesting a positive benefit of SF-Alg as an adjvant agent for T2D.