Li Yuan, Chen Song-Tao, Zhang Yao-Yuan, Qin Jin-Feng, Zhu Xiao, Yin Kai
The Second Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, 541199, Guangxi, China.
Department of General Practice, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, 510900, Guangdong, China.
Metab Brain Dis. 2025 Jan 14;40(1):96. doi: 10.1007/s11011-025-01529-6.
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.
2型糖尿病（T2D）是脑认知功能障碍的一个重要危险因素，但其具体机制仍不清楚。病理条件下肠道微生物群的失衡（如致病菌增加）可能参与多种疾病的发生。本研究的目的是探讨肠道鼠柠檬酸杆菌丰度增加对T2D小鼠认知功能的影响。我们的结果表明，鼠柠檬酸杆菌丰度的增加导致肠道屏障受损、血液和脑组织中炎症因子表达升高，并促进T2D小鼠的认知功能障碍。具体途径涉及法尼醇X受体（FXR）表达介导的肠道屏障功能障碍的激活。使用肠道黏膜保护剂和FXR抑制剂可改善肠道屏障功能和脑认知功能。因此，本研究结果为T2D小鼠肠道中柠檬酸杆菌丰度增加与脑认知功能之间提供了一个机制联系，并为T2D脑认知功能障碍的发生提供了参考。
