1. The Mouse Microbiome Is Required for Sex-Specific Diurnal Rhythms of Gene Expression and Metabolism
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Aline Charpagne, Francis Foata, Jake Yeung, Benjamin D. Weger, Felix Naef, Bertrand Betrisey, Eva Martin, Frédéric Gachon, Aurélie Balvay, Sonia Jimenez, Cédric Gobet, Bernard Berger, Chieh Jason Chou, Anne Foussier, Brigitte Boizet-Bonhoure, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland., Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland, Cellular Metabolism, Department of Cell Biology, Nestlé Institute of Health Sciences, Nestlé Research, 1015 Lausanne, Switzerland., Nestle Res Ctr, Nestec Ltd, Host-Microbe Interaction, Department of Gastro-Intestinal Health, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Genomics, Department of Multi-Omics, Nestlé Institute of Health Sciences, Nestlé Research, 1015 Lausanne, Switzerland, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Nestlé Research Center, Nestle Reasearch Center, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland, 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), Nestlé Research Center | Centre de recherche Nestlé [Lausanne], Nestlé S.A., and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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0301 basic medicine ,Male ,Physiology ,[SDV]Life Sciences [q-bio] ,Circadian clock ,nuclear receptors ,Gene Expression ,White adipose tissue ,Transcriptome ,Mice ,0302 clinical medicine ,circadian clock ,reproductive function ,Sex Characteristics ,sexual maturation ,Growth hormone secretion ,symbiosis ,Cell biology ,Circadian Rhythm ,Intestines ,germ-free ,ghrelin ,Female ,diet-induced obesity ,Adipose Tissue, White ,Feminization (biology) ,Bcl6 ,Biology ,liver ,Article ,03 medical and health sciences ,Circadian Clocks ,Metabolome ,microbiota ,Animals ,Humans ,Microbiome ,Molecular Biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,gut microbiota ,aryl-hydrocarbon receptor ,growth-hormone-secretion ,Cell Biology ,signaling pathways ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Sexual dimorphism ,030104 developmental biology ,cyp1a1 expression ,sexual dimorphism ,growth hormone ,030217 neurology & neurosurgery - Abstract
Summary 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., Graphical Abstract, Highlights • The microbiome is required for sexual dimorphism in gene expression and metabolism • Most already-described changes in GF mice are hallmarks of a feminized metabolism • Altered sexual maturation and GH secretion cause the damping of sexual dimorphism • Microbiota-derived metabolites and ghrelin likely drive these alterations, Physiology is dynamic over the day and different between sexes. Weger et al. show that the microbiome play a key role in sustaining these sex differences in gene expression and metabolism by ensuring proper sexual maturation and growth hormone secretion. Microbiota-derived metabolites and ghrelin likely drive these sexually dimorphic dynamics.
- Published
- 2019
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