biostudies-literatureSteed ALNICHD NIH HHSNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSCrohn’s Colitis498-502https://www.ebi.ac.uk/biostudies/studies/S-EPMC5753406biostudies-literatureUnknown357(6350)The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, <i>Clostridium orbiscindens,</i> produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effeScience (New York, N.Y.)The microbial metabolite desaminotyrosine protects from influenza through type I interferon.PMC5753406R01 AI111605T32 DK007130U19 AI070412U19 AI070489K12 HD000850UH3 HL123429award312855P30 DK056341R01 AI130591Steed ALStappenbeck TSChristophi GPEsaulova EMorales DJSun LArtyomov MNLenschow DJHoltzman MJGoodwin VMKaiko GEJain UBoon ACMfalseThe microbial metabolite desaminotyrosine protects from influenza through type I interferon.The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, <i>Clostridium orbiscindens,</i> produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effe2017-01-01T00:00:00Z2017 Aug2025-04-03T23:18:23.27Z2019-03-27T03:06:22ZS-EPMC57534062877492810.1126/science.aam5336