Causal effects of the gut microbiome on COVID-19 susceptibility and severity: a two-sample Mendelian randomization study

Meng-Mei Zhong; Jia-Hao Xie; Yao Feng; Shao-Hui Zhang; Jiang-Nan Xia; Li Tan; Ning-Xin Chen; Xiao-Lin Su; Qian Zhang; Yun-Zhi Feng; Yue Guo

doi:10.3389/fimmu.2023.1173974

Causal effects of the gut microbiome on COVID-19 susceptibility and severity: a two-sample Mendelian randomization study

Front Immunol. 2023 Sep 1:14:1173974. doi: 10.3389/fimmu.2023.1173974. eCollection 2023.

Authors

Affiliations

¹ Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Institute of Artificial Intelligence & Robotics (IAIR), Key Laboratory of Traffic Safety on Track of Ministry of Education, School of Traffic and Transportation Engineering, Central South University, Changsha, Hunan, China.
³ Department of Stomatology, Xiangyang Central Hospital, Xiangyang, Hubei, China.
⁴ School of Architecture and Art, Central South University, Changsha, Hunan, China.

Abstract

Background: The coronavirus disease 2019 (COVID-19) caused a global pandemic, with potential severity. We aimed to investigate whether genetically predicted gut microbiome is associated with susceptibility and severity of COVID-19 risk.

Methods: Mendelian randomization (MR) analysis of two sets with different significance thresholds was carried out to infer the causal relationship between the gut microbiome and COVID-19. SNPs associated with the composition of the gut microbiome (n = 5,717,754) and with COVID-19 susceptibility (n = 14,328,058), COVID-19 severity (n = 11,707,239), and COVID-19 hospitalization (n = 12,018,444) from publicly available genome-wide association studies (GWAS). The random-effect inverse variance weighted (IVW) method was used to determine causality. Three more MR techniques-MR Egger, weighted median, and weighted mode-and a thorough sensitivity analysis were also used to confirm the findings.

Results: IVW showed that 18 known microbial taxa were causally associated with COVID-19. Among them, six microbial taxa were causally associated with COVID-19 susceptibility; seven microbial taxa were causally associated with COVID-19 severity ; five microbial taxa were causally associated with COVID-19 hospitalization. Sensitivity analyses showed no evidence of pleiotropy or heterogeneity. Then, the predicted 37 species of the gut microbiome deserve further study.

Conclusion: This study found that some microbial taxa were protective factors or risky factors for COVID-19, which may provide helpful biomarkers for asymptomatic diagnosis and potential therapeutic targets for COVID-19.

Keywords: COVID-19; Mendelian randomization; gut microbiome; severity; susceptibility.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / genetics
Causality
Gastrointestinal Microbiome*
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis

Grants and funding

This study was supported by the National Natural Science Foundation of China (81800788 and 81773339), Science and Technology Department of Hunan Province, China (2017WK2041, 2018SK52511, and 2022ZK4084), Scientific Research Project of Hunan Provincial Health Commission (202208043514 and B202308056340), Hunan Provincial Natural Science Foundation of China (2022JJ30062), Natural Science Foundation of Changsha City (kq2202403 and kq2202412), Fund for the Xiangya Clinical Medicine Database of Central South University (2014-ZDYZ-1-16), Education and Teaching Reform Research Project of Central South University (2020jy165-3), Research Project on Postgraduate Education and Teaching Reform of Central South University(2021JGB072), Hunan Provincial Innovation Foundation For Postgraduate (CX20220370), and the Fundamental Research Funds for the Central Universities of Central South University (2022ZZTS0913 and 2022ZZTS0912).