Department of Anesthesiology, Xiangya Hospital Central South University, Changsha 410008, China.
Department of Anesthesiology, Xiangya Hospital Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha 410008, China.
Neurobiol Dis. 2024 Feb;191:106395. doi: 10.1016/j.nbd.2023.106395. Epub 2023 Dec 28.
Emerging evidence has indicated that the alterations in gut microbiota and metabolites are associated with cognitive performance. However, whether these associations imply a causal relationship remains to be definitively established. Here, we conducted two-sample mendelian randomization (MR) studies to explore the causal effects of gut microbiota and metabolites on cognitive performance, using large-scale genome-wide association studies (GWASs). We identified seven positive causalities between host genetic-driven gut microbiota and cognitive performance, including Class Clostridia (p = 0.0002), Order Clostridiales (p = 8.12E-05), Family Rhodospirillaceae (p = 0.042) and Ruminococcustorquesgroup (p = 0.030), Dialister (p = 0.027), Paraprevotella (p = 0.037) and RuminococcaceaeUCG003 (p = 0.007) at the genus level. Additionally, a total of four higher abundance of gut microbiota traits were identified to be negatively related to cognitive performance, including genus Blautia (p = 0.013), LachnospiraceaeFCS020group (p = 0.035), LachnospiraceaeNK4A136group (p = 0.034) and Roseburia (p = 0.00016). In terms of plasma metabolites, we discovered eight positive and six negative relationships between genetic liability in metabolites and cognitive performance (all p < 0.05). No evidence was detected across a series of sensitivity analyses, including pleiotropy and heterogeneity. Collectively, our MR analyses revealed that gut microbiota and metabolites were causally connected with cognitive performance, which holds significant potential for shedding light on the early detection and diagnosis of cognitive impairment, offering valuable insights into this area of research.
新出现的证据表明，肠道微生物群和代谢物的改变与认知表现有关。然而，这些关联是否意味着因果关系仍有待明确确定。在这里，我们进行了两项基于孟德尔随机化（MR）的研究，使用大规模全基因组关联研究（GWAS）来探索肠道微生物群和代谢物对认知表现的因果影响。我们确定了宿主遗传驱动的肠道微生物群与认知表现之间的七种正向因果关系，包括纲梭菌（p=0.0002）、目梭菌目（p=8.12E-05）、科红螺旋菌科（p=0.042）和瘤胃球菌科 Ruminococcustorques 组（p=0.030）、Dialister（p=0.027）、拟普雷沃氏菌属（p=0.037）和瘤胃球菌科 UCG003（p=0.007）在属水平。此外，还确定了四个与认知表现呈负相关的较高丰度的肠道微生物群特征，包括属布劳特氏菌（p=0.013）、LachnospiraceaeFCS020 组（p=0.035）、LachnospiraceaeNK4A136 组（p=0.034）和罗氏菌（p=0.00016）。就血浆代谢物而言，我们发现遗传易感性代谢物与认知表现之间存在八种正相关和六种负相关（均 p<0.05）。在一系列敏感性分析中，包括多效性和异质性，都没有发现证据。总的来说，我们的 MR 分析表明，肠道微生物群和代谢物与认知表现之间存在因果关系，这为认知障碍的早期检测和诊断提供了重要的启示，为该研究领域提供了有价值的见解。
