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^*

^*Corresponding author for this work

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

37 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
Article number	2105609
Journal	Gut Microbes
Volume	14
Issue number	1
DOIs	https://doi.org/10.1080/19490976.2022.2105609
State	Published - 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

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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), Article 2105609. https://doi.org/10.1080/19490976.2022.2105609

@article{c6fb95d21b7042d389bfde54c4017e2e,

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 = "Publisher Copyright: {\textcopyright} 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.",

year = "2022",

doi = "10.1080/19490976.2022.2105609",

language = "אנגלית",

volume = "14",

journal = "Gut Microbes",

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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, 2105609. 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.

PY - 2022

Y1 - 2022

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.

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U2 - 10.1080/19490976.2022.2105609

DO - 10.1080/19490976.2022.2105609

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C2 - 35915556

AN - SCOPUS:85135265171

SN - 1949-0976

VL - 14

JO - Gut Microbes

JF - Gut Microbes

IS - 1

M1 - 2105609

ER -

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

Abstract

Bibliographical note

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