Long-Term Genistein Consumption Modifies Gut Microbiota, Improving Glucose Metabolism, Metabolic Endotoxemia, and Cognitive Function in Mice Fed a High-Fat Diet

Scope: The aim of this study is to assess whether the long-term addition of genistein to a high-fat diet can ameliorate the metabolic and the cognitive alterations and whether the changes can be associated with modifications to the gut microbiota. Methods and results: C57/BL6 mice were fed either a control (C) diet, a high-fat (HF) diet, or a high-fat diet containing genistein (HFG) for 6 months. During the study, indirect calorimetry, IP glucose tolerance tests, and behavioral analyses were performed. At the end of the study, plasma, liver, brain, and fecal samples were collected. The results showed that mice fed the HFG diet gained less weight, had lower serum triglycerides, and an improvement in glucose tolerance than those fed an HF diet. Mice fed the HFG diet also modified the gut microbiota that was associated with lower circulating levels of lipopolysaccharide (LPS) and reduced expression of pro-inflammatory cytokines in the liver compared to those fed HF diet. The reduction in LPS by the consumption of genistein was accompanied by an improvement of the cognitive function. Conclusions: Genistein is able to regulate the gut microbiota, reducing metabolic endotoxemia and decreasing the neuroinflammatory response despite the consumption of a HF diet.