Mouse gut diel study. mouse gut metagenome

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. Here, we implicate an additional key element involved in maintenance of host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, gnotobiotic 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. Exploration of specific microbial metabolites induced under low or high fat feeding, particularly short chain fatty acids or hydrogen sulfide, show direct modulation of circadian clock gene expression within hepatocytes. These results underscore the ability of microbially-derived metabolites to regulate or disrupt circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.