Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism

Cell Host Microbe. 2015 May 13;17(5):681-9. doi: 10.1016/j.chom.2015.03.006. Epub 2015 Apr 16.


Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts. Examination of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.

Publication types

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

MeSH terms

  • Animals
  • Body Weight
  • Circadian Clocks*
  • Diet, High-Fat*
  • Disease Models, Animal
  • Dysbiosis / chemically induced*
  • Gastrointestinal Microbiome*
  • Gastrointestinal Tract / microbiology*
  • Gene Expression Profiling
  • Lipid Metabolism*
  • Liver / pathology
  • Mice
  • Molecular Sequence Data
  • Obesity
  • Sequence Analysis, DNA

Associated data

  • GEO/GSE53590
  • figshare/10.6084/M9.FIGSHARE.882928