Affiliation:
1. Department of Critical Care Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
2. Anhui Medical University Hefei China
Abstract
AbstractEvidence supports the observational associations of gut microbiota with the risk of COVID‐19; however, it is unclear whether these associations reflect a causal relationship. This study investigated the association of gut microbiota with COVID‐19 susceptibility and severity. Data were obtained from a large‐scale gut microbiota data set (n = 18 340) and the COVID‐19 Host Genetics Initiative (n = 2 942 817). Causal effects were estimated with inverse variance weighted (IVW), MR‐Egger, and weighted median, and sensitivity analyses were implemented with Cochran's Q test, MR‐Egger intercept test, MR‐PRESSO, leave‐one‐out analysis, and funnel plots. For COVID‐19 susceptibility, IVW estimates suggested that Gammaproteobacteria (odds ratio [OR] = 0.94, 95% confidence interval [CI], 0.89–0.99, p = 0.0295] and Streptococcaceae (OR = 0.95, 95% CI, 0.92–1.00, p = 0.0287) had a reduced risk, while Negativicutes (OR = 1.05, 95% CI, 1.01–1.10, p = 0.0302), Selenomonadales (OR = 1.05, 95% CI, 1.01–1.10, p = 0.0302), Bacteroides (OR = 1.06, 95% CI, 1.01–1.12, p = 0.0283), and Bacteroidaceae (OR = 1.06, 95% CI, 1.01–1.12, p = 0.0283) were associated with an increased risk (all p < 0.05, nominally significant). For COVID‐19 severity, Subdoligranulum (OR = 0.80, 95% CI, 0.69–0.92, p = 0.0018), Cyanobacteria (OR = 0.85, 95% CI, 0.76–0.96, p = 0.0062), Lactobacillales (OR = 0.87, 95% CI, 0.76–0.98, p = 0.0260), Christensenellaceae (OR = 0.87, 95% CI, 0.77–0.99, p = 0.0384), Tyzzerella3 (OR = 0.89, 95% CI, 0.81–0.97, p = 0.0070), and RuminococcaceaeUCG011 (OR = 0.91, 95% CI, 0.83–0.99, p = 0.0247) exhibited negative correlations, while RikenellaceaeRC9 (OR = 1.09, 95% CI, 1.01–1.17, p = 0.0277), LachnospiraceaeUCG008 (OR = 1.12, 95% CI, 1.00–1.26, p = 0.0432), and MollicutesRF9 (OR = 1.14, 95% CI, 1.01–1.29, p = 0.0354) exhibited positive correlations (all p < 0.05, nominally significant). Sensitivity analyses validated the robustness of the above associations. These findings suggest that gut microbiota might influence the susceptibility and severity of COVID‐19 in a causal way, thus providing novel insights into the gut microbiota‐mediated development mechanism of COVID‐19.
Funder
National Natural Science Foundation of China
Subject
Infectious Diseases,Virology