Lung microbiota dysbiosis exacerbates influenza virus infection

Previous studies have shown that microbiota in the respiratory tract play a significant role in shaping host immunity and reducing the risk of respiratory tract infections. Influenza, an acute respiratory infectious disease caused by the influenza virus (IAV), necessitates to have an in-depth understanding of the pathogenic mechanisms of viral infection and to utilize these mechanisms to prevent and control influenza infection. In this study, we established models of different disease severity levels in mice infected with IAV, the relationships between changes in pulmonary microbiota and host interactions during IAV infection were analyzed. We found that these relationships were characterized by the enrichment of opportunistic pathogenic taxonomic groups and were related to disease severity. Multi-omics analysis combined with animal experiments clarified that colonization of Bacillus cereus in the lungs aggravates IAV infection through xanthosine, thereby downregulating the expression of nt5e and reducing the viral phagocytic ability of alveolar macrophages. Importantly, targeted removal of B. cereus by bacteriophages can alleviate IAV infection and the resulting pulmonary lesions. Highlighting provides a novel approach for preventing and controlling the progression of IAV infection by targeting the lung microbiota. Lung dysbiosis is associated with severe influenza virus (IAV) infection. Bacillus cereus aggravates IAV infection via the xanthosine-nt5e axis in SPF mice, which can be rescued by bacteriophage targeting. These findings highlight the potential of modulating the lung microbiota as a strategy for prevention and controlling IAV infection.