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

被引:39
作者
Brown, Julia A. [1 ,2 ]
Sanidad, Katherine Z. [1 ,2 ]
Lucotti, Serena [1 ,2 ]
Lieber, Carolin M. [3 ]
Cox, Robert M. [3 ]
Ananthanarayanan, Aparna [1 ,2 ]
Basu, Srijani [4 ]
Chen, Justin [1 ]
Shan, Mengrou [5 ]
Amir, Mohammed [1 ,2 ]
Schmidt, Fabian [6 ]
Weisblum, Yiska [6 ]
Cioffi, Michele [1 ,2 ]
Li, Tingting [7 ]
Rowdo, Florencia Madorsky [8 ]
Martin, M. Laura [8 ]
Guo, Chun-Jun [7 ]
Lyssiotis, Costas [4 ]
Layden, Brian T. [9 ,10 ]
Dannenberg, Andrew J. [4 ]
Bieniasz, Paul D. [6 ,11 ]
Lee, Benhur [12 ]
Inohara, Naohiro [5 ]
Matei, Irina [1 ,2 ]
Plemper, Richard K. [3 ]
Zeng, Melody Y. [1 ,2 ]
机构
[1] Weill Cornell Med, Gale & Ira Drukier Inst Childrens Hlth, New York, NY 10021 USA
[2] Weill Cornell Med, Dept Pediat, New York, NY 10021 USA
[3] Georgia State Univ, Inst Biomed Sci, Atlanta, GA 30303 USA
[4] Weill Cornell Med, Dept Med, New York, NY USA
[5] Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USA
[6] Rockefeller Univ, Lab Retrovirol, 1230 York Ave, New York, NY 10021 USA
[7] Weill Cornell Med, Jill Roberts Inst Inflammatory Bowel Dis, New York, NY USA
[8] Weill Cornell Med, Englander Inst Precis Med, New York, NY USA
[9] Univ Illinois, Dept Med, Div Endocrinol Diabet & Metab, Chicago, IL USA
[10] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA
[11] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[12] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
基金
美国国家卫生研究院;
关键词
CHAIN FATTY-ACIDS; ACE2; MEGAKARYOCYTES; REPLICATION; RESPONSES; ANTIBODY; IMMUNITY; PROTEIN; HEALTH; CELLS;
D O I
10.1080/19490976.2022.2105609
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
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页数:22
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