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

来源：

GUT MICROBES | 2022年 / 14卷 / 01期

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

页数：22

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