The Mouse Microbiome Is Required for Sex-Specific Diurnal Rhythms of Gene Expression and Metabolism
2019
Weger, Benjamin | Gobet, Cédric | Yeung, Jake | Martin, Eva | Jimenez, Sonia | Betrisey, Bertrand | Foata, Francis | Berger, Bernard | Balvay, Aurélie | Foussier, Anne | Charpagne, Aline | Boizet-Bonhoure, Brigitte | Chou, Chieh Jason | Naef, Felix | Gachon, Frederic | Nestlé Institute of Health Sciences SA [Lausanne, Switzerland] | Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne] (CHUV) | Ecole Polytechnique Fédérale de Lausanne (EPFL) | Nestlé Research Center | Centre de recherche Nestlé [Lausanne] ; Nestlé S.A. | Host-Microbe Interaction, Department of Gastro-Intestinal Health ; Nestlé Institute of Health Sciences SA [Lausanne, Switzerland] | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech | Institut de génétique humaine (IGH) ; Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) | Swiss National Science Foundation [310030_173079]; Natural Sciences and Engineering Research Council of Canada Postgraduate Studies Doctoral Scholarship | European Project: 260988,EC:FP7:ERC,ERC-2010-StG_20091118,CIRCATRANS(2011)
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Show more [+] Less [-]English. The circadian clock and associated feeding rhythms have a profound impact on metabolism and the gut microbiome. To what extent microbiota reciprocally affect daily rhythms of physiology in the host remains elusive. Here, we analyzed transcriptome and metabolome profiles of male and female germ-free mice. While mRNA expression of circadian clock genes revealed subtle changes in liver, intestine, and white adipose tissue, germ-free mice showed considerably altered expression of genes associated with rhythmic physiology. Strikingly, the absence of the microbiome attenuated liver sexual dimorphism and sex-specific rhythmicity. The resulting feminization of male and masculinization of female germ-free animals is likely caused by altered sexual development and growth hormone secretion, associated with differential activation of xenobiotic receptors. This defines a novel mechanism by which the microbiome regulates host metabolism.
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