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PMID: 30344015 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Mouse Microbiome Is Required for Sex-Specific Diurnal Rhythms of Gene Expression and Metabolism.

Cell metabolism ·Vol. 29 ·No. 2 ·2019-00-05 ·Pages 362-382.e8

Weger BD, Gobet C, Yeung J, Martin E, Jimenez S, Betrisey B, Foata F, Berger B, Balvay A, Foussier A, Charpagne A, Boizet-Bonhoure B, Chou CJ, Naef F, Gachon F

Abstract

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.

Keywords
Bcl6 circadian clock ghrelin growth hormone liver microbiota sexual dimorphism sexual maturation symbiosis
MeSH Terms
Adipose Tissue, White/metabolism Animals Circadian Clocks Circadian Rhythm Female Gastrointestinal Microbiome Ghrelin/metabolism Intestines/microbiology Liver/metabolism Male Mice Mice, Inbred C57BL Sex Characteristics Transcriptome
Chemicals
Ghrelin
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Weger Benjamin D
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland.
Gobet Cédric
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland; Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Yeung Jake
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Martin Eva
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland.
Jimenez Sonia
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland.
Betrisey Bertrand
Cellular Metabolism, Department of Cell Biology, Nestlé Institute of Health Sciences, Nestlé Research, 1015 Lausanne, Switzerland.
Foata Francis
Host-Microbe Interaction, Department of Gastro-Intestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, 1000 Lausanne, Switzerland.
Berger Bernard
Host-Microbe Interaction, Department of Gastro-Intestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, 1000 Lausanne, Switzerland.
Balvay Aurélie
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
Foussier Anne
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
Charpagne Aline
Genomics, Department of Multi-Omics, Nestlé Institute of Health Sciences, Nestlé Research, 1015 Lausanne, Switzerland.
Boizet-Bonhoure Brigitte
Institut de Génétique Humaine, CNRS-Université de Montpellier UMR9002, 34396 Montpellier, France.
Chou Chieh Jason
Host-Microbe Interaction, Department of Gastro-Intestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, 1000 Lausanne, Switzerland.
Naef Felix
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Gachon Frédéric
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: f.gachon@uq.edu.au.
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Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1932-7420
DOI
10.1016/j.cmet.2018.09.023
Email
f.gachon@uq.edu.au
Published
2019-00-05
Epub
2018-00-18
Pages
362-382.e8
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC6370974
Subset
IM
Corrections
CommentIn
PMID: 30425340
External Links
PubMed source DOI: 10.1016/j.cmet.2018.09.023 PMC Full Text View journal details
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