{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T03:38:01Z","timestamp":1772249881958,"version":"3.50.1"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["320.6750.2021-16-32"],"award-info":[{"award-number":["320.6750.2021-16-32"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-006104"],"award-info":[{"award-number":["INV-006104"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 <jats:italic>p<\/jats:italic>-value was used. To test the robustness of the causal relationships with <jats:italic>p<\/jats:italic>-FDR &amp;lt; 0.05, sensitivity analyses including the secondary MR analyses, horizontal pleiotropy test, outliers test, and \u201cleave-one-out\u201d analysis were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 <jats:italic>Alloprevotella<\/jats:italic> [odds ratio (OR) = 1.67; 95% confidence interval (95% CI), 1.32\u20132.11; <jats:italic>p<\/jats:italic> = 1.69\u00d710<jats:sup>\u22125<\/jats:sup>, <jats:italic>p<\/jats:italic>-FDR = 2.01\u00d710<jats:sup>\u22123<\/jats:sup>] 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 <jats:italic>Bacteroidetes<\/jats:italic> (OR = 1.13; 95% CI, 1.04\u20131.22; <jats:italic>p<\/jats:italic> = 3.02\u00d710<jats:sup>\u22123<\/jats:sup>; <jats:italic>p<\/jats:italic>-FDR = 2.72\u00d710<jats:sup>\u22122<\/jats:sup>). However, secondary MR analyses indicated that the result of COVID-19 hospitalization on the phylum <jats:italic>Bacteroidetes<\/jats:italic> required careful consideration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed the causal association between gut microbiome and COVID-19 and highlighted the role of \u201cgut-lung axis\u201d in the progression of COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1217615","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T09:04:32Z","timestamp":1688720672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic support of the causal association between gut microbiome and COVID-19: a bidirectional Mendelian randomization study"],"prefix":"10.3389","volume":"14","author":[{"given":"Zengbin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guixian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangye","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqiong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyao","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingwang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingqin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01585-9","article-title":"The 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