Fucoidan from Laminaria japonica Ameliorates Type 2 Diabetes Mellitus in Association with Modulation of Gut Microbiota and Metabolites in Streptozocin-Treated Mice

Chronic diseases have been a leading cause of death worldwide, and polysaccharide supplementation is an effective therapeutic strategy for chronic diseases without adverse effects. In this study, the beneficial effect of Laminaria japonica fucoidan (LJF) on type 2 diabetes mellitus (T2DM) was evaluated in streptozocin-treated mice. LJF ameliorated the symptoms of T2DM in a dose-dependent manner, involving reduction in weight loss, water intake, triglyceride, blood glucose, cholesterol and free fatty acids, and increases in high-density lipoprotein cholesterol, catalase, glucagon-like peptide-1, and superoxide dismutase. In addition, LJF regulated the balance between insulin resistance and insulin sensitivity, reduced islet necrosis and β-cell damage, and inhibited fat accumulation in T2DM mice. The protective effect of LJF on T2DM can be associated with modulation of the gut microbiota and metabolites, e.g., increases in Lactobacillus and Allobaculum. Untargeted and targeted metabolomics analysis showed that the microbiota metabolite profile was changed with LJF-induced microbiota alterations, mainly involving amino acids, glutathione, and glyoxylate and dicarboxylate metabolism pathways. This study indicates that LJF can be used as a prebiotic agent for the prevention and treatment of diabetes and microbiota-related diseases.