Polysaccharide from Oyster ( Crassostrea gigas ) Alleviates T2DM by Regulating the Gut Microbiota, Bile Acid Metabolism, and the PI3K/AKT Pathway

Abstract Hyperglycemia has become a global public health crisis, yet effective intervention strategies for type 2 diabetes mellitus (T2DM) remain poorly characterized. This study explored the hypoglycemic effects of oyster polysaccharides (OP) in T2DM mice and the underlying mechanisms centered on the gut microbiota–bile acid axis. The results showed that OP significantly modulated glucose and lipid metabolism disorders in T2DM mice, improved pancreatic, hepatic, and colonic tissue damage, and suppressed inflammatory responses. 16S rRNA gene sequencing indicated that OP reshaped the gut microbial community and enriched bile salt hydrolase-producing bacteria. Consistently, OP remodeled the fecal bile acid pool, which further coordinated hepatic FXR/TGR5 signaling to maintain glucose homeostasis. Additionally, OP activated the hepatic PI3K/AKT cascade to promote glycogen synthesis and inhibit excessive gluconeogenesis. The present work elucidated the antidiabetic capacity of OP from the gut microbiota–bile acid regulatory axis, providing a novel mechanistic insight into its hypoglycemic activity.