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. 2022 Dec 13;41(11):111755.
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

Mao Hagihara  1 , Makoto Yamashita  2 , Tadashi Ariyoshi  3 , Shuhei Eguchi  4 , Ayaka Minemura  4 , Daiki Miura  4 , Seiya Higashi  4 , Kentaro Oka  3 , Tsunemasa Nonogaki  5 , Takeshi Mori  2 , Kenta Iwasaki  6 , Jun Hirai  2 , Yuichi Shibata  7 , Takumi Umemura  2 , Hideo Kato  8 , Nobuhiro Asai  2 , Yuka Yamagishi  2 , Akinobu Ota  9 , Motomichi Takahashi  3 , Hiroshige Mikamo  10
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Free article

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

Mao Hagihara et al. Cell Rep. .
Free article

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.

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Conflict of interest statement

Declaration of interests M.T., K.O., T.A., S.E., A.M., D.M., and S.H. are employees of MIYARISAN Pharmaceutical Co., Ltd. H.M. received research funding from Asahi Kasei Pharma Corporation; FUJIFILM Toyama Chemical Co., Ltd.; Miyarisan Pharmaceutical Co., Ltd.; Shionogi & Co. Ltd.; Daiichi Sankyo Co., Ltd.; Pfizer Japan Inc.; and Sumitomo Dainippon Pharma Co., Ltd. and honorarium/consulting fees from Astellas Pharma Inc.; Becton, Dickinson and Company Japan; Daiichi Sankyo Co., Ltd.; FUJIFILM Toyama Chemical Co. Ltd.; MIYARISAN Pharmaceutical Co., Ltd.; MSD K.K.; and Sumitomo Dainippon Pharma Co., Ltd.

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