Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection

The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) is not fully understood. Severe and fatal COVID-19 is characterized by poor anti-viral immunity and hypercoagulation, particularly in males. Here, we define multiple p...

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Main Authors: Julia A. Brown, Katherine Z. Sanidad, Serena Lucotti, Carolin M. Lieber, Robert M. Cox, Aparna Ananthanarayanan, Srijani Basu, Justin Chen, Mengrou Shan, Mohammed Amir, Fabian Schmidt, Yiska Weisblum, Michele Cioffi, Tingting Li, Florencia Madorsky Rowdo, M. Laura Martin, Chun-Jun Guo, Costas A. Lyssiotis, Brian T. Layden, Andrew J. Dannenberg, Paul D. Bieniasz, Benhur Lee, Naohiro Inohara, Irina Matei, Richard K. Plemper, Melody Y. Zeng
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2105609
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Summary:The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) is not fully understood. Severe and fatal COVID-19 is characterized by poor anti-viral immunity and hypercoagulation, particularly in males. Here, we define multiple pathways by which the gut microbiome protects mammalian hosts from SARS-CoV-2 intranasal infection, both locally and systemically, via production of short-chain fatty acids (SCFAs). SCFAs reduced viral burdens in the airways and intestines by downregulating the SARS-CoV-2 entry receptor, angiotensin-converting enzyme 2 (ACE2), and enhancing adaptive immunity via GPR41 and 43 in male animals. We further identify a novel role for the gut microbiome in regulating systemic coagulation response by limiting megakaryocyte proliferation and platelet turnover via the Sh2b3-Mpl axis. Taken together, our findings have unraveled novel functions of SCFAs and fiber-fermenting gut bacteria to dampen viral entry and hypercoagulation and promote adaptive antiviral immunity.
ISSN:1949-0976
1949-0984