TY - JOUR
T1 - Genetic support of the causal association between gut microbiome and COVID-19
T2 - a bidirectional Mendelian randomization study
AU - Li, Zengbin
AU - Zhu, Guixian
AU - Lei, Xiangye
AU - Tang, Liqiong
AU - Kong, Guangyao
AU - Shen, Mingwang
AU - Zhang, Lei
AU - Song, Lingqin
N1 - Publisher Copyright:
Copyright © 2023 Li, Zhu, Lei, Tang, Kong, Shen, Zhang and Song.
PY - 2023
Y1 - 2023
N2 - Background: The association between gut microbiome and coronavirus disease 2019 (COVID-19) has attracted much attention, but its causality remains unclear and requires more direct evidence. Methods: In this study, we conducted the bidirectional Mendelian randomization (MR) analysis to assess the causal association between gut microbiome and COVID-19 based on the summary statistics data of genome-wide association studies (GWASs). Over 1.8 million individuals with three COVID-19 phenotypes (severity, hospitalization and infection) were included. And 196 bacterial taxa from phylum to genus were analyzed. The inverse-variance weighted (IVW) analysis was chosen as the primary method. Besides, false discovery rate (FDR) correction of p-value was used. To test the robustness of the causal relationships with p-FDR < 0.05, sensitivity analyses including the secondary MR analyses, horizontal pleiotropy test, outliers test, and “leave-one-out” analysis were conducted. Results: In the forward MR, we found that 3, 8, and 10 bacterial taxa had suggestive effects on COVID-19 severity, hospitalization and infection, respectively. The genus Alloprevotella [odds ratio (OR) = 1.67; 95% confidence interval (95% CI), 1.32–2.11; p = 1.69×10−5, p-FDR = 2.01×10−3] was causally associated with a higher COVID-19 severity risk. In the reverse MR, COVID-19 severity, hospitalization and infection had suggestive effects on the abundance of 4, 8 and 10 bacterial taxa, respectively. COVID-19 hospitalization causally increased the abundance of the phylum Bacteroidetes (OR = 1.13; 95% CI, 1.04–1.22; p = 3.02×10−3; p-FDR = 2.72×10−2). However, secondary MR analyses indicated that the result of COVID-19 hospitalization on the phylum Bacteroidetes required careful consideration. Conclusion: Our study revealed the causal association between gut microbiome and COVID-19 and highlighted the role of “gut-lung axis” in the progression of COVID-19.
AB - Background: The association between gut microbiome and coronavirus disease 2019 (COVID-19) has attracted much attention, but its causality remains unclear and requires more direct evidence. Methods: In this study, we conducted the bidirectional Mendelian randomization (MR) analysis to assess the causal association between gut microbiome and COVID-19 based on the summary statistics data of genome-wide association studies (GWASs). Over 1.8 million individuals with three COVID-19 phenotypes (severity, hospitalization and infection) were included. And 196 bacterial taxa from phylum to genus were analyzed. The inverse-variance weighted (IVW) analysis was chosen as the primary method. Besides, false discovery rate (FDR) correction of p-value was used. To test the robustness of the causal relationships with p-FDR < 0.05, sensitivity analyses including the secondary MR analyses, horizontal pleiotropy test, outliers test, and “leave-one-out” analysis were conducted. Results: In the forward MR, we found that 3, 8, and 10 bacterial taxa had suggestive effects on COVID-19 severity, hospitalization and infection, respectively. The genus Alloprevotella [odds ratio (OR) = 1.67; 95% confidence interval (95% CI), 1.32–2.11; p = 1.69×10−5, p-FDR = 2.01×10−3] was causally associated with a higher COVID-19 severity risk. In the reverse MR, COVID-19 severity, hospitalization and infection had suggestive effects on the abundance of 4, 8 and 10 bacterial taxa, respectively. COVID-19 hospitalization causally increased the abundance of the phylum Bacteroidetes (OR = 1.13; 95% CI, 1.04–1.22; p = 3.02×10−3; p-FDR = 2.72×10−2). However, secondary MR analyses indicated that the result of COVID-19 hospitalization on the phylum Bacteroidetes required careful consideration. Conclusion: Our study revealed the causal association between gut microbiome and COVID-19 and highlighted the role of “gut-lung axis” in the progression of COVID-19.
KW - COVID-19
KW - Mendelian randomization
KW - SARS-CoV-2
KW - causality
KW - gut microbiota
KW - randomized controlled trial
KW - rct
UR - https://www.scopus.com/pages/publications/85165247486
U2 - 10.3389/fimmu.2023.1217615
DO - 10.3389/fimmu.2023.1217615
M3 - 文章
C2 - 37483615
AN - SCOPUS:85165247486
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1217615
ER -