The causal role of gut microbiota in susceptibility and severity of COVID‐19: A bidirectional Mendelian randomization study

Abstract

Growing evidence has shown that altered gut microbiota is associated with the pathogenesis of COVID‐19, but their causal effects are still unclear. We conducted a bidirectional Mendelian randomization (MR) study to assess the causal effects of gut microbiota on COVID‐19 susceptibility or severity, and vice versa. The microbiome genome‐wide association studies (GWAS) data of 18 340 individuals and GWAS statistics from the COVID‐19 host genetics initiative (38 984 European patients and 1 644 784 controls) were used as exposure and outcomes. The inverse variance weighted (IVW) was used as the primary MR analysis. Sensitivity analyses were performed to validate the robustness, pleiotropy, and heterogeneity of results. In the forward MR, we identified several microbial genera with causal effects on COVID‐19 susceptibility (p < 0.05 and FDR < 0.1): Alloprevotella (odds ratio [OR]: 1.088, 95% confidence interval [CI]: 1.021–1.160), Coprococcus (OR: 1.159, 95% CI: 1.030–1.304), Parasutterella (OR: 0.902, 95% CI: 0.836–0.973), and Ruminococcaceae UCG014 (OR: 0.878, 95% CI: 0.777–0.992). The Reverse MR identified that exposure to COVID‐19 had causal effects on the depletion of the families Lactobacillaceae (Beta [SE]: −0.220 [0.101]) and Lachnospiraceae (−0.129 [0.062]), the genera Flavonifractor (−0.180 [0.081]) and Lachnoclostridium [−0.181 [0.063]). Our findings supported the causal effect of gut microbiota on the pathogenesis of COVID‐19, and infection of COVID‐19 might further causally induce gut microbiota dysbiosis.

Exploring gut–lung axis crosstalk in SARS‐CoV‐2 infection: Insights from a hACE2 mouse model

“…Of particular interest, a bidirectional Mendelian randomization study suggests that Alloprevotella may increase COVID-19 susceptibility, while SARS-CoV-2 infection causally leads to the depletion of the Lachnospiraceae family. 42 To predict the potential roles of these altered bacterial species in regulating hyperinflammatory responses to SARS-CoV-2 infection, Spearman's correlation analysis was conducted. Notably, Lachnospiraceae_NK4A136_group and unclassified_f_ Lachnospiraceae are speculated to have anti-inflammatory effects based on experimental data.…”

Causal associations of gut microbiota and pulmonary tuberculosis: a two-sample Mendelian randomization study

“…Our study identified a causal association between three gut microbiota, namely Parasutterella, Dorea, and Lachnoclostridium, and PTB. Notably, Parasutterella has been found to have a causal relationship with various other conditions in several Mendelian randomization studies, including COVID-19 ( Chen H. et al, 2023 ), intrahepatic cholangiocarcinoma (ICC) ( Chen Z. et al, 2023 ), chronic kidney disease (CKD) ( Ren et al, 2023 ), and prostatitis ( Shen et al, 2024 ). Meanwhile, Dorea is associated with autism spectrum disorder (ASD) ( Li Z. et al, 2023 ), inflammatory bowel disease (IBD) ( Zhang et al, 2021 ), hypertensive disorders in pregnancy (HDP) ( Wu et al, 2023a ), polycystic ovary syndrome (PCOS) ( Min et al, 2023 ), hemorrhagic stroke ( Shen et al, 2023 ), age-related macular degeneration (AMD) ( Li and Lu, 2023 ), nicotine dependence ( Chen Y. et al, 2023 ), and insomnia ( Li Z. et al, 2023 ).…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…These findings suggest that the gut microbiota may have a causal relationship with the severity of COVID‐19, thus providing new evidence and ideas for the study of the pathogenesis of SARS‐CoV‐2 mediated by gut microbiota. 107 , 108 …”