Li Xiao, Ren Yueran, Gao Xuxuan, Wang Huidi, Zhang Jiafeng, Xie Jiahui, Liang Jingru, Zhao Boxin, Zhou Hongwei, Yin Jia
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
J Cereb Blood Flow Metab. 2025 May;45(5):989-1004. doi: 10.1177/0271678X241309777. Epub 2024 Dec 24.
Chronic cerebral hypoperfusion (CCH) is a crucial mechanism causing vascular cognitive impairment (VCI). Choline is metabolized by gut microbiota into trimethylamine N-oxide (TMAO), a risk factor of cardiovascular diseases and cognitive impairment. However, the impact of choline-TMAO pathway on CCH-induced VCI is elusive. We performed a cross-sectional clinical study to investigate the relationship between the choline-TMAO pathway and cognitive outcome and used a bilateral common carotid artery occlusion rat model to explore the effect of a choline-rich diet on cognition and underlying mechanisms. Plasma choline and TMAO levels were negatively correlated with cognitive scores in CCH patients. A choline-rich diet exacerbated CCH-induced cognitive impairment by encouraging the proliferation of choline-metabolizing bacteria in the gut and subsequent generation of TMAO. The choline-TMAO pathway, mediated by gut microbiota, exacerbates cognitive impairment induced by CCH. Targeted dietary choline regulation based on gut microbiota modulation may ameliorate long-term cognitive impairment.
慢性脑灌注不足（CCH）是导致血管性认知障碍（VCI）的关键机制。胆碱被肠道微生物群代谢为氧化三甲胺（TMAO），后者是心血管疾病和认知障碍的一个风险因素。然而，胆碱-TMAO途径对CCH诱导的VCI的影响尚不清楚。我们进行了一项横断面临床研究，以调查胆碱-TMAO途径与认知结果之间的关系，并使用双侧颈总动脉闭塞大鼠模型来探讨富含胆碱的饮食对认知及潜在机制的影响。CCH患者的血浆胆碱和TMAO水平与认知评分呈负相关。富含胆碱的饮食通过促进肠道中胆碱代谢细菌的增殖以及随后TMAO的生成，加剧了CCH诱导的认知障碍。由肠道微生物群介导的胆碱-TMAO途径会加剧CCH诱导的认知障碍。基于肠道微生物群调节的靶向饮食胆碱调节可能会改善长期认知障碍。
