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. 2025 May;45(5):989-1004.
doi: 10.1177/0271678X241309777. Epub 2024 Dec 24.

Gut microbiota-mediated choline metabolism exacerbates cognitive impairment induced by chronic cerebral hypoperfusion

Xiao Li  1 , Yueran Ren  1 , Xuxuan Gao  1 , Huidi Wang  2 , Jiafeng Zhang  1 , Jiahui Xie  1 , Jingru Liang  1 , Boxin Zhao  3   4 , Hongwei Zhou  2 , Jia Yin  1
Affiliations

Gut microbiota-mediated choline metabolism exacerbates cognitive impairment induced by chronic cerebral hypoperfusion

Xiao Li et al. J Cereb Blood Flow Metab. 2025 May.

Abstract

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.

Keywords: Choline; chronic cerebral hypoperfusion; cognitive impairment; gut microbiota; trimethylamine N-oxide.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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