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

Cell. 2021 Aug 5;184(16):4154-4167.e12. doi: 10.1016/j.cell.2021.07.001. Epub 2021 Jul 28.


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.

Keywords: Antimicrobial proteins; circadian clock; feeding rhythms; foodborne pathogen; innate immunity; innate lymphoid cells; intestine; microbiota.

Publication types

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

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Bacterial Adhesion
  • Cell Adhesion
  • Circadian Clocks / physiology*
  • Circadian Rhythm / physiology*
  • Epithelial Cells / microbiology
  • Feeding Behavior
  • Gastrointestinal Microbiome*
  • Immunity, Innate*
  • Intestine, Small / microbiology
  • Intestine, Small / ultrastructure
  • Lymphocytes / metabolism
  • Mice, Inbred C57BL
  • Muramidase / metabolism
  • Pancreatitis-Associated Proteins / metabolism
  • STAT3 Transcription Factor / metabolism
  • Salmonella Infections, Animal / microbiology
  • Signal Transduction


  • Antimicrobial Cationic Peptides
  • Pancreatitis-Associated Proteins
  • Reg3g protein, mouse
  • STAT3 Transcription Factor
  • Muramidase