Citrobacter rodentium promotes brain cognitive dysfunction of type 2 diabetes mice by activating FXR mediated gut barrier damage.

Abstract

Type 2 diabetes (T2D) is an important risk factor for brain cognitive impairment, but the specific mechanism is still unclear. The imbalance of gut microbiota under pathological conditions (such as an increase in pathogenic bacteria) may be involved in the occurrence of various diseases. The purpose of this study is to investigate the effect of increased abundance of gut Citrobacter rodentium on cognitive function in T2D mice. Our results indicate that an increase in the abundance of Citrobacter rodentium leads to impaired intestinal barrier, elevated expression of inflammatory factors in blood and brain tissue, and promotes cognitive impairment in T2D mice. The specific pathway involves activation of farnesol X receptor (FXR) expression-mediated intestinal barrier dysfunction. The use of intestinal mucosal protectants and FXR inhibitors improved intestinal barrier function and brain cognitive function. Therefore, the research results provide a mechanistic link between the increased abundance of Citrobacter in the gut of T2D mice and brain cognitive function, and provide a reference for the occurrence of brain cognitive dysfunction in T2D.