Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia

Journal of Neuroinflammation

Zhenhuang Zhuang¹  Ruotong Yang¹  Wenxiu Wang¹  Tao Huang²  Lu Qi³ 

[1] Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, 100191, Beijing, China;Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, 100191, Beijing, China;Department of Global Health, School of Public Health, Peking University, 100191, Beijing, China;Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, 100191, Beijing, China;Center for Intelligent Public Health, Institute for Artificial Intelligence, Peking University, 100191, Beijing, China;Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA;Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;

关键词: Gut microbiota;    Neuropsychiatric disorder;    Mendelian randomization;    Genetic association;    Causality;   

DOI  :  10.1186/s12974-020-01961-8

来源: Springer

【 摘 要 】

BackgroundGrowing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer’s disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ).MethodsA two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively.ResultsWe found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79–0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92–1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00–1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83–0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00–1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02–1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition.ConclusionsThese data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.

【 授权许可】

CC BY