Large-scale genetic correlation studies explore the causal relationship and potential mechanism between gut microbiota and COVID-19-associated risks

作者全名："Li, He; Wen, Jie; Zhang, Xiangbin; Dai, Ziyu; Liu, Mingren; Zhang, Hao; Zhang, Nan; Lei, Ruoyan; Luo, Peng; Zhang, Jingwei"

作者地址："[Li, He] Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Anim Lab Ctr,Xiangya Sch Med, Changsha, Peoples R China; [Wen, Jie; Dai, Ziyu; Liu, Mingren; Zhang, Jingwei] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China; [Wen, Jie; Dai, Ziyu; Liu, Mingren; Zhang, Jingwei] Cent South Univ, Xiangya Hosp, Hypothalam Pituitary Res Ctr, Changsha, Peoples R China; [Wen, Jie; Zhang, Xiangbin; Dai, Ziyu; Liu, Mingren; Zhang, Jingwei] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China; [Zhang, Xiangbin] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha, Hunan, Peoples R China; [Zhang, Hao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Zhang, Nan] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan, Peoples R China; [Lei, Ruoyan] Cent South Univ, Xiangya Sch Publ Hlth, Changsha, Peoples R China; [Luo, Peng] Southern Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou, Peoples R China"

通信作者："Zhang, JW (通讯作者)，Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China.; Zhang, JW (通讯作者)，Cent South Univ, Xiangya Hosp, Hypothalam Pituitary Res Ctr, Changsha, Peoples R China.; Zhang, JW (通讯作者)，Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.; Luo, P (通讯作者)，Southern Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou, Peoples R China."

来源：BMC MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001285379800001

JCR分区：Q2

影响因子：4.2

年份：2024

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：COVID-19; Gut microbiota; Mendelian randomization; Mediation analysis

摘要："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."

基金机构：High-Performance Computing Center of Central South University

基金资助正文："The authors express gratitude to the public databases, websites, and software used in the paper. The authors are grateful to the High-Performance Computing Center of Central South University for partial support of this work."