Temporal profile of Liver of Cry1/2 double knockout (DKO) mice. Temporal profile of Liver of Cry1/2 double knockout (DKO) mice

Gut microbiota and the circadian clock both regulate metabolism. The circadian clock and associated feeding rhythms were shown to impact on the microbial community. However, to what extent gut microbiota reciprocally affect daily rhythms of gene expression and physiology in the host remains elusive. Here, we analyzed the transcriptomes of male and female germ-free mice. While this revealed subtle changes in circadian clock gene expression in liver, intestine, and white adipose tissue, germ-free mice showed considerably altered expression of genes associated to rhythmic physiology. Strikingly, absence of microbiome severely compromised liver sex-dimorphism at the transcriptome and metabolome level. Their sex-specific rhythmicity was strongly attenuated. The resulting feminization of male and masculinization of female hepatic gene expression in germ-free animals is likely caused by altered sex-dimorphism in sex and growth hormone secretion, linked to differential activation of xenobiotic receptors. This defines a novel mechanism by which the gut microbiome regulates host metabolism. Overall design: Total RNA-Seq of night fed Cry1/2 DKO male mice. Temporal mRNA profiles of liver were assessed every 4 hours during a diurnal cycle (Zeitgerber time (ZT) 2-22). Night fed wild-type animals corresponding to the Cry1/2 DKO series are available under the accession numbers: GSM1897844-GSM1897855.