SRP125796 PRJNA419862 feces metagenome Raw sequence reads Commensal microbiota play an important role in many physiological processes. Importantly, they pose a natural threshold to colonization with pathogenic bacteria by direct competition. Here we show that acute infection of the lung with influenza A viruses causes elimination of a substantial proportion of bacteria from the small intestine. This weakens the natural shield against pathogenic bacteria and renders the intestinal epithelium vulnerable for invading bacteria. We further show that influenza A virus infection up-regulates the activity of Paneth cells a major source of antimicrobial peptides in the small intestine. This suggests that influenza A viruses affect a host mechanism of microbiota regulation to cause bacterial depletion in the small intestine. Surprisingly, the same mechanism does not apply in the respiratory tract, where influenza A virus infection causes subtle qualitative but not quantitative changes in the commensal microbiota. Overall, our date provide the first description of microbiota dynamics in an acute infection animal model. feces metagenome pubmed 29321057