Purpose: Genistein (GEN) has been reported to have diverse biological activities, including antioxidant, hypolipidemic, and antidiabetic effects. This study investigated whether the ameliorative effects of GEN on inflammation and insulin resistance were associated with the modulation of gut microbiota composition in type 2 diabetic (T2D) mice.
Methods: C57BL/6J mice were treated with a high-fat diet/streptozotocin to induce T2D and then gavaged with GEN (20 and 40 mg/kg) for 8 weeks. Then, oral glucose tolerance, fasting blood glucose, serum insulin, glucagon, lipid profiles, and pro-inflammatory factors were measured. After this, hepatic function and histopathological analysis and inflammation-related indices of the liver and colon were determined, along with short-chain fatty acid (SCFA) and gut microbiota composition.
Results: GEN treatment decreased hyperglycemia, hyperlipidemia, and serum pro-inflammatory factor levels and attenuated hepatic dysfunction, pathological changes, inflammation-related protein expression, and hepatocyte apoptosis. It also ameliorated colonic pathological changes, tight junction-associated protein expression, and pro-inflammatory factor increases. Furthermore, high-dose GEN treatment increased the concentrations of SCFAs and down-regulated the ratio of Firmicutes/Bacteroidetes and the abundance of Proteobacteria at the phylum level. However, GEN increased the abundances of Bacteroides and Prevotella and decreased the levels of Helicobacter and Ruminococcus at the genus level in T2D mice.
Conclusion: GEN showed ameliorative effects on glucose and lipid dysmetabolism and hepatic and colonic dysfunction; most importantly, GEN could ameliorate inflammation and insulin resistance through modulation of gut microbiota composition.
Keywords: Diabetes; Genistein; Gut microbiota; Inflammation; Insulin resistance.