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

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.