Large-scale genetic correlation studies explore the causal relationship and potential mechanism between gut microbiota and COVID-19-associated risks
He Li, Jie Wen, Xiangbin Zhang, Ziyu Dai, Mingren Liu, Hao Zhang, Nan Zhang, Ruoyan Lei, Peng Luo, Jingwei Zhang
BMC Microbiology, 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 , 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.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12866-024-03423-0. Supplementary Material 1.
Supplementary Material 2. Authors' contributions JW-Z and PL conceived, designed, and funded the research. JW-Z and JW wrote the first draft of the manuscript. HL, JW-Z, JW, XB-Z, ZY-D, HZ, NZ, RY-L, PL, and MR-L contributed to data acquisition, analysis, and interpretation. HL, JW-Z, JW,XB-Z, ZY-D, HZ, NZ, RY-L, PL, and MR-L contributed to the revision of the paper. All authors contributed to the article and approved the final manuscript.
Declarations Ethics approval and consent to participate All data used by this study were publicly available from participant studies with the approvement of the ethical standards committee related to human experimentation. No additional ethical approval was required in this study.
Consent for publication Not applicable.
Competing interests The authors declare no competing interests.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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