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

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 Lyssiotis, Brian T. Layden, Andrew J. DannenbergPaul D. Bieniasz, Benhur Lee, Naohiro Inohara, Irina Matei, Richard K. Plemper, Melody Y. Zeng

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.
Original languageEnglish (US)
JournalGut Microbes
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2022
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Gastroenterology
  • Microbiology

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