The precise mechanism by which butyrate-producing bacteria in the gut contribute to resistance to respiratory viral infections remains to be elucidated. Here, we elucidate a new lung-gut 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 to the IFN regulatory factor (IRF)-1/-7 pathway. CB promotes 18-HEPE production in the gut and enhances ω-3 fatty acid sensitivity in the lungs by promoting GPR120 expression through modulation of the lung microbiome. In parallel, CB-producing proteins increase Bifidobacterium species in the lungs, resulting in the promotion of GPR120 expression in lung epithelial cells. Therefore, this study revealed a novel gut-lung axis mechanism and provides new insights into the treatments and prophylaxis for viral respiratory infections.
Hagihara, Mao and Yamashita, Makoto and Ariyoshi, Tadashi and Eguchi, Shuhei and Minemura, Ayaka and Miura, Daiki and Higashi, Seiya and Oka, Kentaro and Nonogaki, Tsunemasa and Mori, Takeshi and Iwasaki, Kenta and Hirai, Jun and Shibata, Yuichi and Umemura, Takumi and Kato, Hideo and Asai, Nobuhiro and Yamagishi, Yuka and Ota, Akinobu and Takahashi, Motomichi and Mikamo, Hiroshige, Gut Microbiome-Induced ω-3 Fatty Acid, 18-HEPE, Elicits Anti-Influenza Virus Pneumonia Effects Through Interferon-λ Upregulation. Available at SSRN: https://ssrn.com/abstract=4089980 or http://dx.doi.org/10.2139/ssrn.4089980
This version of the paper has not been formally peer reviewed.
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