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

Julia A. Brown; Katherine Z. Sanidad; Serena Lucotti; Carolin M. Lieber; Robert M. Cox; Aparna Ananthanarayanan; Srijani Basu; Justin Chen; Mengrou Shan; Mohammed Amir; Fabian Schmidt; Yiska Weisblum; Michele Cioffi; Tingting Li; Florencia Madorsky Rowdo; M. Laura Martin; Chun Jun Guo; Costas Lyssiotis; Brian T. Layden; Andrew J. Dannenberg; Paul D. Bieniasz; Benhur Lee; Naohiro Inohara; Irina Matei; Richard K. Plemper; Melody Y. Zeng

doi:10.1080/19490976.2022.2105609

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

Julia A. Brown, Katherine Z. Sanidad, Serena Lucotti, Carolin M. Lieber, Robert M. Cox, Aparna Ananthanarayanan, Srijani Basu, Justin Chen, Mengrou Shan, Mohammed Amir, Fabian Schmidt, Yiska Weisblum, Michele Cioffi, Tingting Li, Florencia Madorsky Rowdo, M. Laura Martin, Chun Jun Guo, Costas Lyssiotis, Brian T. Layden, Andrew J. DannenbergPaul D. Bieniasz, Benhur Lee, Naohiro Inohara, Irina Matei, Richard K. Plemper, Melody Y. Zeng

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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.

Original language	English (US)
Journal	Gut Microbes
Volume	14
Issue number	1
DOIs	https://doi.org/10.1080/19490976.2022.2105609
State	Published - Jan 1 2022
Externally published	Yes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases
Gastroenterology
Microbiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/19490976.2022.2105609

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Brown, J. A., Sanidad, K. Z., Lucotti, S., Lieber, C. M., Cox, R. M., Ananthanarayanan, A., Basu, S., Chen, J., Shan, M., Amir, M., Schmidt, F., Weisblum, Y., Cioffi, M., Li, T., Rowdo, F. M., Martin, M. L., Guo, C. J., Lyssiotis, C., Layden, B. T., ... Zeng, M. Y. (2022). Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection. Gut Microbes, 14(1). https://doi.org/10.1080/19490976.2022.2105609

@article{895474a5c7034dea9ae4bba70f96cc79,

title = "Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection",

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.",

author = "Brown, {Julia A.} and Sanidad, {Katherine Z.} and Serena Lucotti and Lieber, {Carolin M.} and Cox, {Robert M.} and Aparna Ananthanarayanan and Srijani Basu and Justin Chen and Mengrou Shan and Mohammed Amir and Fabian Schmidt and Yiska Weisblum and Michele Cioffi and Tingting Li and Rowdo, {Florencia Madorsky} and Martin, {M. Laura} and Guo, {Chun Jun} and Costas Lyssiotis and Layden, {Brian T.} and Dannenberg, {Andrew J.} and Bieniasz, {Paul D.} and Benhur Lee and Naohiro Inohara and Irina Matei and Plemper, {Richard K.} and Zeng, {Melody Y.}",

note = "Generated from Scopus record by KAUST IRTS on 2023-02-15",

year = "2022",

month = jan,

day = "1",

doi = "10.1080/19490976.2022.2105609",

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Brown, JA, Sanidad, KZ, Lucotti, S, Lieber, CM, Cox, RM, Ananthanarayanan, A, Basu, S, Chen, J, Shan, M, Amir, M, Schmidt, F, Weisblum, Y, Cioffi, M, Li, T, Rowdo, FM, Martin, ML, Guo, CJ, Lyssiotis, C, Layden, BT, Dannenberg, AJ, Bieniasz, PD, Lee, B, Inohara, N, Matei, I, Plemper, RK & Zeng, MY 2022, 'Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection', Gut Microbes, vol. 14, no. 1. https://doi.org/10.1080/19490976.2022.2105609

TY - JOUR

T1 - Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection

AU - Brown, Julia A.

AU - Sanidad, Katherine Z.

AU - Lucotti, Serena

AU - Lieber, Carolin M.

AU - Cox, Robert M.

AU - Ananthanarayanan, Aparna

AU - Basu, Srijani

AU - Chen, Justin

AU - Shan, Mengrou

AU - Amir, Mohammed

AU - Schmidt, Fabian

AU - Weisblum, Yiska

AU - Cioffi, Michele

AU - Li, Tingting

AU - Rowdo, Florencia Madorsky

AU - Martin, M. Laura

AU - Guo, Chun Jun

AU - Lyssiotis, Costas

AU - Layden, Brian T.

AU - Dannenberg, Andrew J.

AU - Bieniasz, Paul D.

AU - Lee, Benhur

AU - Inohara, Naohiro

AU - Matei, Irina

AU - Plemper, Richard K.

AU - Zeng, Melody Y.

N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15

PY - 2022/1/1

Y1 - 2022/1/1

N2 - 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.

AB - 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.

UR - https://www.tandfonline.com/doi/full/10.1080/19490976.2022.2105609

UR - http://www.scopus.com/inward/record.url?scp=85135265171&partnerID=8YFLogxK

U2 - 10.1080/19490976.2022.2105609

DO - 10.1080/19490976.2022.2105609

M3 - Article

C2 - 35915556

SN - 1949-0976

VL - 14

JO - Gut Microbes

JF - Gut Microbes

IS - 1

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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