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

TitleGut microbiota-derived metabolites confer protection against SARS-CoV-2 infection.
Publication TypeJournal Article
Year of Publication2022
AuthorsBrown JA, Sanidad KZ, Lucotti S, Lieber CM, Cox RM, Ananthanarayanan A, Basu S, Chen J, Shan M, Amir M, Schmidt F, Weisblum Y, Cioffi M, Li T, Rowdo FMadorsky, M Martin L, Guo C-J, Lyssiotis C, Layden BT, Dannenberg AJ, Bieniasz PD, Lee B, Inohara N, Matei I, Plemper RK, Zeng MY
JournalGut Microbes
Date Published2022 Jan-Dec
KeywordsAnimals, Antiviral Agents, COVID-19, Fatty Acids, Volatile, Gastrointestinal Microbiome, Male, Mammals, Peptidyl-Dipeptidase A, SARS-CoV-2

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.

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Alternate JournalGut Microbes
PubMed ID35915556
PubMed Central IDPMC9348133
Grant ListK01 DK114376 / DK / NIDDK NIH HHS / United States
DP2 HD101401 / HD / NICHD NIH HHS / United States
R01 HL148271 / HL / NHLBI NIH HHS / United States
U01 DK127378 / DK / NIDDK NIH HHS / United States
I01 BX003382 / BX / BLRD VA / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
R01 DK104927 / DK / NIDDK NIH HHS / United States
TL1 TR002386 / TR / NCATS NIH HHS / United States

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