Journal Article

Gut microbiome, cognitive function and brain structure: a multi-omics integration analysis

Zhang, Ke, Chen, Yu-ming, Lin, Hong-rou, Jiang, Zengliang, Zhang, Bing, Gou, Wanglong, Liu, Chun-ying, Chen, Shengdi, Fu, Yuanqing, Miao, Zelei, Jia, Xiaofang, Cao, Wen-ting, Huang, Yujing, Wang, Zhihong, Zhong, Haili, Shuai, Menglei, Liang, Xinxiu, Zheng, Ju-Sheng

2022

Overview

Background Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. Methods We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer’s disease case–control study (replication study 1, n  = 90) and another community-based cohort (replication study 2, n  = 1300) with cross-sectional dataset. Results We found protective associations of specific gut microbial genera ( Odoribacter , Butyricimonas , and Bacteroides ) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06–0.26, P  = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. Conclusions Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Alzheimer's disease / Biomedical and Life Sciences / Biomedicine / Body mass index / Brain - diagnostic imaging / Brain structure / Case-Control Studies / Cognition / Cognition & reasoning / Cognitive ability / Cognitive impairment / Cohort / Cross-Sectional Studies / Cytokines / Dementia / Digestive system / Feces / Gastrointestinal Microbiome - genetics / Gut microbiome / Gut microbiota / Gut-brain axis / Humans / Magnetic resonance imaging / Megacities / Metabolites / Metagenomics / Microbiome–gut–brain axis / Microbiota / Mitochondria Dysfunctions and Neurodegenerative Diseases / Neurology / Neurosciences / Pathogenesis / Regression analysis / RNA, Ribosomal, 16S - genetics / Software / Statistical analysis