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Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection [RNA-Seq]

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 in male animals. In order to identify other mechanisms by which SCFAs influence the outcome of SARS-CoV-2 infection, we performed RNA-seq on lungs from male GF mice given control or SCFA water for two weeks. We identified 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 that might be leveraged as pan-coronavirus therapeutics to dampen viral entry and hypercoagulation and promote adaptive anti-viral immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE189792 | GEO | 2022/08/02

REPOSITORIES: GEO

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