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

• Published in: Cell reports (Cambridge) 2022-12, Vol.41 (11), p.111755-111755, Article 111755
• Main Authors: Hagihara, Mao, Yamashita, Makoto, Ariyoshi, Tadashi, Eguchi, Shuhei, Minemura, Ayaka, Miura, Daiki, Higashi, Seiya, Oka, Kentaro, Nonogaki, Tsunemasa, Mori, Takeshi, Iwasaki, Kenta, Hirai, Jun, Shibata, Yuichi, Umemura, Takumi, Kato, Hideo, Asai, Nobuhiro, Yamagishi, Yuka, Ota, Akinobu, Takahashi, Motomichi, Mikamo, Hiroshige
• Format: Article
• Language: English
• Subjects: 18-hydroxy eicosapentaenoic acid; Clostridium butyricum; Clostridium butyricum - metabolism; Fatty Acids, Omega-3 - metabolism; G protein-coupled receptor 120; Humans; influenza virus; Interferon Lambda; interferon-λ; mouse pneumonia; Orthomyxoviridae Infections; Up-Regulation; ω-3 fatty acid
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111755

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. [Display omitted] •Oral administration of Clostridium butyricum attenuates influenza virus pneumonia•Clostridium butyricum-induced IFN-λ can enhance influenza virus infection resistance•Orally administered Clostridium butyricum enhances 18-HEPE production in the gut•18-HEPE upregulates IFN-λ in lungs through GPR120 and IRF-1/-7 activation Hagihara et al. show that orally administered butyrate-producing Clostridium butyricum (CB) enhances influenza virus infection resistance through interferon (IFN)-λ upregulation in lung epithelial cells. A gut microbe-induced ω-3 fatty acid, 18-hydroxy eicosapentaenoic acid (18-HEPE), promotes IFN-λ production through G protein-coupled receptor (GPR)120 and IFN regulatory factor (IRF)-1/-7 activation.