| Literature DB >> 35915556 |
Julia A Brown1,2, Katherine Z Sanidad1,2, Serena Lucotti1,2, Carolin M Lieber3, Robert M Cox3, Aparna Ananthanarayanan1,2, Srijani Basu4, Justin Chen1, Mengrou Shan5, Mohammed Amir1,2, Fabian Schmidt6, Yiska Weisblum6, Michele Cioffi1,2, Tingting Li7, Florencia Madorsky Rowdo8, M Laura Martin8, Chun-Jun Guo7, Costas Lyssiotis4, Brian T Layden9,10, Andrew J Dannenberg4, Paul D Bieniasz6,11, Benhur Lee12, Naohiro Inohara5, Irina Matei1,2, Richard K Plemper3, Melody Y Zeng1,2.
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.Entities:
Mesh：
Substances：
Year: 2022 PMID： 35915556 PMCID： PMC9348133 DOI： 10.1080/19490976.2022.2105609
Source DB: PubMed Journal: Gut Microbes ISSN： 1949-0976