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

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

PROVIDER: PRJNA784538 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17065816_1.fastq.gz	Fastqsanger.gz
	SRR17065816_2.fastq.gz	Fastqsanger.gz
	SRR17065817_1.fastq.gz	Fastqsanger.gz
	SRR17065817_2.fastq.gz	Fastqsanger.gz
	SRR17065818_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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