Clostridium butyricum-altered lung microbiome is associated with enhanced anti-influenza effects via G-protein-coupled receptor120

We previously reported that orally administered <i>Clostridium butyricum</i> enhances anti-influenza virus effects through the interferon-λ upregulation in mice lungs; however, the precise mechanism remains unclear. Orally administered <i>C. butyricum</i> promotes the proliferation of <i>Bifidobacterium</i> species in the lung microbiome, and this enhances <i>C. butyricum</i> induced anti-influenza effects. Among the <i>Bifidobacterium</i> species, <i>B. longum</i> effectively enhanced the sensitivity of the lung epithelial cells to long-chain fatty acids through the G-protein-coupled receptor120 upregulation. Oral administration of <i>C. butyricum</i> altered long-chain fatty acid metabolism and promoted interferon-λ production through G-protein-coupled receptor120. We hypothesized that these effects enhance anti-influenza virus responses through interferon-λ upregulation via collaboration between long-chain fatty acid metabolism alterations and the lung microbiome moderation. This study identified a gut-lung axis mechanism and provides insights into viral respiratory infection treatment and prophylaxis.