Clostridium butyricum-induced ω-3 fatty acid 18-HEPE elicits anti-influenza virus pneumonia effects through interferon-λ upregulation

Mao Hagihara; Makoto Yamashita; Tadashi Ariyoshi; Shuhei Eguchi; Ayaka Minemura; Daiki Miura; Seiya Higashi; Kentaro Oka; Tsunemasa Nonogaki; Takeshi Mori; Kenta Iwasaki; Jun Hirai; Yuichi Shibata; Takumi Umemura; Hideo Kato; Nobuhiro Asai; Yuka Yamagishi; Akinobu Ota; Motomichi Takahashi; Hiroshige Mikamo

doi:10.1016/j.celrep.2022.111755

Clostridium butyricum-induced ω-3 fatty acid 18-HEPE elicits anti-influenza virus pneumonia effects through interferon-λ upregulation

Cell Rep. 2022 Dec 13;41(11):111755. doi: 10.1016/j.celrep.2022.111755.

Authors

Mao Hagihara¹, Makoto Yamashita², Tadashi Ariyoshi³, Shuhei Eguchi⁴, Ayaka Minemura⁴, Daiki Miura⁴, Seiya Higashi⁴, Kentaro Oka³, Tsunemasa Nonogaki⁵, Takeshi Mori², Kenta Iwasaki⁶, Jun Hirai², Yuichi Shibata⁷, Takumi Umemura², Hideo Kato⁸, Nobuhiro Asai², Yuka Yamagishi², Akinobu Ota⁹, Motomichi Takahashi³, Hiroshige Mikamo¹⁰

Affiliations

¹ Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute 480-1195, Japan; Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan.
² Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan.
³ Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan; R&D Division, Miyarisan Pharmaceutical Co., Ltd., Saitama 331-0804, Japan.
⁴ R&D Division, Miyarisan Pharmaceutical Co., Ltd., Saitama 331-0804, Japan.
⁵ Department of Pharmacy, College of Pharmacy Kinjo Gakuin University, Nagoya 463-8521, Japan.
⁶ Departments of Kidney Disease and Transplant Immunology, Aichi Medical University, Nagakute 480-1195, Japan.
⁷ Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute 480-1195, Japan.
⁸ Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan; Department of Pharmacy, Mie University Hospital, Tsu, Mie, Japan.
⁹ Departments of Biochemistry, Aichi Medical University, Nagakute 480-1195, Japan.
¹⁰ Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan. Electronic address: mikamo@aichi-med-u.ac.jp.

PMID: 36516771
DOI: 10.1016/j.celrep.2022.111755

Abstract

The precise mechanism by which butyrate-producing bacteria in the gut contribute to resistance to respiratory viral infections remains to be elucidated. Here, we describe a gut-lung axis mechanism and report that orally administered Clostridium butyricum (CB) enhances influenza virus infection resistance through upregulation of interferon (IFN)-λ in lung epithelial cells. Gut microbiome-induced ω-3 fatty acid 18-hydroxy eicosapentaenoic acid (18-HEPE) promotes IFN-λ production through the G protein-coupled receptor (GPR)120 and IFN regulatory factor (IRF)-1/-7 activations. CB promotes 18-HEPE production in the gut and enhances ω-3 fatty acid sensitivity in the lungs by promoting GPR120 expression. This study finds a gut-lung axis mechanism and provides insights into the treatments and prophylaxis for viral respiratory infections.

Keywords: 18-hydroxy eicosapentaenoic acid; CP: Immunology; CP: Microbiology; Clostridium butyricum; G protein-coupled receptor 120; influenza virus; interferon-λ; mouse pneumonia; ω-3 fatty acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Clostridium butyricum* / metabolism
Fatty Acids, Omega-3* / metabolism
Humans
Interferon Lambda
Orthomyxoviridae Infections*
Up-Regulation

Substances

Interferon Lambda
Fatty Acids, Omega-3