The microbial metabolite desaminotyrosine protects from influenza through type I interferon

Science. 2017 Aug 4;357(6350):498-502. doi: 10.1126/science.aam5336.


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, Clostridium orbiscindens, 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 effects on responses to lethal infections through modulation of type I IFN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Clostridium perfringens / metabolism*
  • GTP-Binding Proteins / genetics
  • Gastrointestinal Microbiome / immunology*
  • Host-Pathogen Interactions / immunology
  • Interferon Type I / immunology*
  • Lung / immunology
  • Mice
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology*
  • Phenylpropionates / immunology*
  • Phenylpropionates / metabolism
  • Signal Transduction


  • Ifi1 protein, mouse
  • Interferon Type I
  • Phenylpropionates
  • phloretic acid
  • GTP-Binding Proteins