The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock

John F. Brooks, Cassie L. Behrendt, Kelly A. Ruhn, Syann Lee, Prithvi Raj, Joseph S. Takahashi, Lora V. Hooper

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Environmental light cycles entrain circadian feeding behaviors in animals that produce rhythms in exposure to foodborne bacteria. Here, we show that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. Rhythmic expression of antimicrobial proteins was driven by daily rhythms in epithelial attachment by segmented filamentous bacteria (SFB), members of the mouse intestinal microbiota. Rhythmic SFB attachment was driven by the circadian clock through control of feeding rhythms. Mechanistically, rhythmic SFB attachment activated an immunological circuit involving group 3 innate lymphoid cells. This circuit triggered oscillations in epithelial STAT3 expression and activation that produced rhythmic antimicrobial protein expression and caused resistance to Salmonella Typhimurium infection to vary across the day-night cycle. Thus, host feeding rhythms synchronize with the microbiota to promote rhythms in intestinal innate immunity that anticipate exogenous microbial exposure.

Original languageEnglish (US)
Pages (from-to)4154-4167.e12
Issue number16
StatePublished - Aug 5 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


  • Antimicrobial proteins
  • circadian clock
  • feeding rhythms
  • foodborne pathogen
  • innate immunity
  • innate lymphoid cells
  • intestine
  • microbiota


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