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.
【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Adaptive immunity, Coronavirus disease 2019, ACE2, adaptive, Immunity, immune regulation, Infection, gut microbiome, angiotensin-converting enzyme 2, viral entry, metabolism, airway, Coagulation, intestine, male, Microbiome, Platelet, short-chain fatty acids, antiviral immunity, intranasal, function, Fatty acid, Angiotensin-converting enzyme, Hypercoagulation, angiotensin, Gut, airways, proliferation, enzyme, entry receptor, intestines, SARS-CoV-2 entry receptor, viral burden, multiple pathways, fatal COVID-19, gut bacteria, mammalian, Anti-viral immunity, Host, fiber, SCFAs, males, Sh2b3, PROTECT, identify, reduced, characterized, promote, systemically, downregulating, multiple pathway, SCFA, the SARS-CoV-2, 【제목키워드】 SARS-COV-2 infection, metabolite,