@article{0734f7dfbb484fbc99a804c396983b1e,
title = "Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection",
abstract = "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.",
author = "Brown, {Julia A.} and Sanidad, {Katherine Z.} and Serena Lucotti and Lieber, {Carolin M.} and Cox, {Robert M.} and Aparna Ananthanarayanan and Srijani Basu and Justin Chen and Mengrou Shan and Mohammed Amir and Fabian Schmidt and Yiska Weisblum and Michele Cioffi and Tingting Li and Rowdo, {Florencia Madorsky} and Martin, {M. Laura} and Guo, {Chun Jun} and Costas Lyssiotis and Layden, {Brian T.} and Dannenberg, {Andrew J.} and Bieniasz, {Paul D.} and Benhur Lee and Naohiro Inohara and Irina Matei and Plemper, {Richard K.} and Zeng, {Melody Y.}",
note = "Funding Information: This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases [K01 DK114376] and funds from the Gale and Ira Drukier Institute for Children{\textquoteright}s Health and Children{\textquoteright}s Health Council at Weill Cornell Medicine, seed grants from the Center for Immunology and Office of Academic Integration of Cornell University and Center for IBD Research at Weill Cornell Medicine, and the Hartwell Foundation (all to MYZ), a CTSC TL1 Scholar Award at Weill Cornell Medicine (award number TL1TR002386) and the Biocodex MicrobiotaFoundation Grant (to JAB), and a postdoctoral fellowship from the HartwellFoundation (to KZS). BTL is supported by NIH(R01DK104927, R01HL148271, U01DK127378, P30DK020595, and the Department of Veterans Affairs(I01BX003382). CJG is supported by the AGA Research Foundation, WCM-RAPPInitiative, the. W. M. Keck Foundation, and the National Institutes of Health (DP2HD101401-01). The authors thank G.F. Sonnenberg for a critical review of the manuscript, R. Pinefor for from the Weill Cornell Gnotobiotic Animal Facility for assistance with gnotobiotic animal studies, and T. Miller for assistance with flow cytometry. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2022",
doi = "10.1080/19490976.2022.2105609",
language = "English",
volume = "14",
journal = "Gut Microbes",
issn = "1949-0976",
publisher = "Landes Bioscience",
number = "1",
}