期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 87, 期 1, 页码 211-222出版社
IOS PRESS
DOI: 10.3233/JAD-215411
关键词
Alzheimer's disease; amyotrophic lateral sclerosis; gastrointestinal microbiome; mendelian randomization analysis; Parkinson's disease
资金
- National Natural Science Foundation of China [820 71201, 82071201]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute
- State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University
This study used Mendelian randomization to evaluate the causal relationships between gut microbiota, metabolites, and neurodegenerative diseases. The findings identified specific gut microbiota and metabolites that were associated with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.
Background: Recent studies had explored that gut microbiota was associated with neurodegenerative diseases (including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS)) through the gut-brain axis, among which metabolic pathways played an important role. However, the underlying causality remained unclear. Objective: Our study aimed to evaluate potential causal relationships between gut microbiota, metabolites, and neurodegenerative diseases through Mendelian randomization (MR) approach. Methods: We selected genetic variants associated with gut microbiota traits (N= 18,340) and gut microbiota-derived metabolites (N= 7,824) from genome-wide association studies. Summary statistics of neurodegenerative diseases were obtained from IGAP (AD, 17,008 cases; 37,154 controls), IPDGC (PD, 37,688 cases; 141,779 controls), and IALSC (ALS, 20,806 cases; 59,804 controls) respectively. Results: Greater abundance of Ruminococcus (OR, 1.245; 95%CI, 1.103-1.405;p = 0.0004) was found significantly related to higher risk of ALS. Besides, our study found suggestive associations of Actinobacteria, Lactobacillaceae, Faecalibacterium, Ruminiclostridium, and Lachnoclostridium with AD, of Lentisphaerae, Lentisphaeria, Oxalobacteraceae, Victivallales, Bacillales, Eubacteriumhalliigroup, Anaerostipes, and Clostridiumsensustricto 1 with PD, and of Lachnospira, Fusicatenibacter, Catenibacterium, and Ruminococcusgnavusgroup with ALS. Our study also revealed suggestive associations between 12 gut microbiome-dependent metabolites and neurodegenerative diseases. Glutamine was related to lower risk of AD. For the serotonin pathway, serotonin was found as a protective factor of PD, while kynurenine as a risk factor for ALS. Conclusion: Our study firstly applied a two-sample MR approach to detect causal relationships among gut microbiota, gut metabolites, and neurodegenerative diseases. Our findings may provide new targets for treatments and may offer valuable insights for further studies on the underlying mechanisms.
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