The Animal Laboratory Center, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
BMC Microbiol. 2024 Aug 5;24(1):292. doi: 10.1186/s12866-024-03423-0.
Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota (n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity (n = 1,086,211), hospitalization (n = 2,095,324), and susceptibility (n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.
最近的观察性研究表明，肠道微生物群与 2019 年冠状病毒病（COVID-19）的发病和发展有关，但它们之间的潜在因果关系尚不清楚。暴露数据来自 MiBioGen 联盟，包含 211 种肠道微生物群（n=18340）。结果数据来源于 COVID-19 宿主遗传学倡议（第 7 轮），包括 COVID-19 严重程度（n=1086211）、住院（n=2095324）和易感性（n=2597856）。首先，进行了两样本 Mendelian 随机化（TSMR）分析，以研究肠道微生物群与 COVID-19 结果之间的因果关系。其次，采用两步 MR 方法探讨潜在的介导因素和潜在机制。第三，进行了几项敏感性分析以验证结果的稳健性。发现五种肠道微生物与 COVID-19 严重程度有潜在的因果关系，即贝塔变形菌（beta=0.096，p=0.034）、克里斯滕森菌科（beta=-0.092，p=0.023）、埃尔德雷奇氏菌（beta=0.072，p=0.048）、粪球菌 1（beta=0.089，p=0.032）和伊森伯格氏菌（beta=0.064，p=0.024）。发现七种肠道微生物与 COVID-19 住院有潜在的因果关系，即 Victivallaceae（beta=0.037，p=0.028）、放线菌科（beta=0.047，p=0.046）、粪球菌 2（beta=-0.061，p=0.031）、Dorea（beta=0.067，p=0.016）、消化球菌科（beta=-0.035，p=0.049）、Rikenellaceae RC9 肠道群（beta=0.034，p=0.018）和变形菌门（beta=-0.069，p=0.035）。发现两种肠道微生物与 COVID-19 易感性有潜在的因果关系，即霍尔德曼氏菌（beta=-0.024，p=0.023）和lachnospiraceae FCS020 组（beta=0.026，p=0.027）。多组学中介分析表明，许多血浆蛋白、代谢物和免疫因子是连接肠道微生物群与 COVID-19 结果的关键介导因素。敏感性分析表明没有显著的异质性或多效性。这些发现揭示了肠道微生物群与 COVID-19 结果之间的因果关系和潜在机制，这可能有助于我们未来更好地理解 COVID-19 发病机制中的肠道-肺部轴。
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