학술논문
Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection
Document Type
article
Author
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
Source
Gut Microbes, Vol 14, Iss 1 (2022)
Subject
Language
English
ISSN
19490976
1949-0984
1949-0976
1949-0984
1949-0976
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.