Faecalibacterium duncaniae, a novel probiotic, shows promise in combating influenza. The study demonstrates that supplementation with live F. duncaniae strains, such as A2-165 and I-4574, reduces influenza severity, lowers viral load, and decreases lung inflammation in mice. These effects are associated with restored levels of short-chain fatty acids (SCFAs), including butyrate, and improved gut microbiota composition. Live F. duncaniae is more effective than pasteurized forms in mitigating influenza outcomes. The probiotic also partially protects against secondary bacterial infections. The findings suggest that F. duncaniae could serve as a next-generation probiotic for viral respiratory diseases. The study highlights the importance of the gut-lung axis in influenza pathogenesis and the potential of microbiome-based therapies. F. duncaniae's protective effects are not strain-specific and involve enhanced type III IFN production. The probiotic restores SCFA levels, which are crucial for immune regulation and viral control. The study also shows that F. duncaniae reduces systemic bacterial translocation after influenza. These results indicate that F. duncaniae could be a valuable tool in preventing and managing influenza and related complications. The study underscores the need for further research into the mechanisms of F. duncaniae's protective effects and its potential applications in clinical settings.Faecalibacterium duncaniae, a novel probiotic, shows promise in combating influenza. The study demonstrates that supplementation with live F. duncaniae strains, such as A2-165 and I-4574, reduces influenza severity, lowers viral load, and decreases lung inflammation in mice. These effects are associated with restored levels of short-chain fatty acids (SCFAs), including butyrate, and improved gut microbiota composition. Live F. duncaniae is more effective than pasteurized forms in mitigating influenza outcomes. The probiotic also partially protects against secondary bacterial infections. The findings suggest that F. duncaniae could serve as a next-generation probiotic for viral respiratory diseases. The study highlights the importance of the gut-lung axis in influenza pathogenesis and the potential of microbiome-based therapies. F. duncaniae's protective effects are not strain-specific and involve enhanced type III IFN production. The probiotic restores SCFA levels, which are crucial for immune regulation and viral control. The study also shows that F. duncaniae reduces systemic bacterial translocation after influenza. These results indicate that F. duncaniae could be a valuable tool in preventing and managing influenza and related complications. The study underscores the need for further research into the mechanisms of F. duncaniae's protective effects and its potential applications in clinical settings.