Mediation of Regional Cerebral Blood Flow in the Relationship between Specific Gut Microbiota and Cognition in Vascular Cognitive Impairment

Article type: Research Article

Authors: Li, Wenyi^{a; b; 1} | Jiang, Jiwei^{a; b; 1} | Yin, Xiangchang^c | Zhang, Yuan^{a; b} | Zou, Xinying^{a; b} | Sun, Mengfan^{a; b} | Jia, Jianjun^d | Ma, Baiping^{c; *} | Xu, Jun^{a; b; *}

Affiliations: [a] Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China | [b] China National Clinical Research Center for Neurological Diseases, Beijing, China | [c] Beijing Institute of Radiation Medicine, Beijing, China | [d] Department of Geriatric Neurology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China

Correspondence: [*] Jun Xu, PhD, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Number 119 South Fourth Ring Road, Fengtai District, Beijing, 100071, China. E-mail: neurojun@126.com and Baiping Ma, PhD, Beijing Institute of Radiation Medicine, Beijing, 100850, China. E-mail: mabaiping@sina.com.

Note: [1] These authors have contributed equally to this work.

Abstract: Background: Gut microbiota could affect the onset and development of vascular cognitive impairment (VCI) through modulating metabolic and immune pathways. However, the vascular mechanisms involved remain unclear. Objective: To investigate the gut microbiota associated with VCI and examine the mediating effects of regional cerebral blood flow (CBF) to explore potential therapeutic targets for VCI. Methods: This prospective study enrolled patients with VCI (n = 16) and healthy controls (n = 18) from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1 and June 30, 2022. The gut microbiota composition and diversity were determined by 16 S ribosomal RNA gene sequencing. The association between gut microbiota and Montreal Cognitive Assessment (MoCA) scores was determined using Spearman’s correlation analysis. Regional CBF was calculated using pseudo-continuous arterial spin labeling. The mediating effects of regional CBF on the relationship between specific gut microbiota and cognition in VCI were investigated using mediation analysis. Results: Compared to healthy controls, patients with VCI had significantly greater abundance of Bifidobacterium, Veillonella, R uminococcus gnavus , Fusobacterium, and Erysipelatoclostridium and smaller abundance of Collinsella. The abundance of Ruminococcus gnavus was negatively associated with MoCA scores in patients with VCI, with the CBF in the left hypothalamus, right hypothalamus, and left amygdala accounting for 63.96%, 48.22%, and 36.51%, respectively, of this association after adjusting for confounders. Conclusions:Ruminococcus gnavus is associated with cognition in VCI, which is strongly mediated by CBF in the bilateral hypothalamus and left amygdala. These findings highlight the potential regulatory roles of nutrition and metabolism-related areas of the brain in VCI.

Keywords: Alzheimer’s disease, cerebral blood flow, cerebral small vessel diseases, gut microbiota, mediation analysis, Ruminococcus gnavus

DOI: 10.3233/JAD-230709

Journal: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 435-445, 2024