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
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.