Cited by 561Circadian rhythm and melatoninGut microbiota and healthImmune Response and Inflammation

Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs

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Mukherji, Atish, Kobiita, Ahmad, Ye, Tao, Chambon, Pierre·2013·Cell

Abstract

Alterations of symbiosis between microbiota and intestinal epithelial cells (IEC) are associated with intestinal and systemic pathologies. Interactions between bacterial products (MAMPs) and Toll-like receptors (TLRs) are known to be mandatory for IEC homeostasis, but how TLRs may time homeostatic functions with circadian changes is unknown. Our functional and molecular dissections of the IEC circadian clock demonstrate that its integrity is required for microbiota-IEC dialog. In IEC, the antiphasic expression of the RORα activator and RevErbα repressor clock output regulators generates a circadian rhythmic TLR expression that converts the temporally arrhythmic microbiota signaling into circadian rhythmic JNK and IKKβ activities, which prevents RevErbα activation by PPARα that would disrupt the circadian clock. Moreover, through activation of AP1 and NF-κB, these activities, together with RORα and RevErbα, enable timing homeostatic functions of numerous genes with IEC circadian events. Interestingly, microbiota signaling deficiencies induce a prediabetic syndrome due to ileal corticosterone overproduction consequent to clock disruption.

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Crossref · 10.1016/j.cell.2013.04.020

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  • There is only preliminary evidence that under basal conditions the GM contributes to the regulation of intestinal glucocorticoid production.

    “However, there is only preliminary evidence available demonstrating that under basal conditions the GM contributes to the regulation of intestinal glucocorticoid production (527, 528).”

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Authors
Mukherji, A., Kobiita, A., Ye, T., & Chambon, P.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Chambon, Pierre
Venue
Cell
Publisher
Elsevier BV
Published
2013-05
Volume
153
Issue
4
Pages
812-827
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2051984731
Cited by
560
References
61
Citations by year
2026: 21 · 2025: 36 · 2024: 45 · 2023: 43 · 2022: 58 · 2021: 43 · 2020: 54 · 2019: 68 · 2018: 24 · 2017: 48 · 2016: 39 · 2015: 39 · 2014: 37 · 2013: 5
FWCI
21.63
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Centre National de la Recherche Scientifique
  • Agence Nationale de la Recherche (07-Physio 002-01)
  • Institut National de la Santé et de la Recherche Médicale
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
intestinal epithelium, circadian clock, gut microbiota, Toll-like receptors, RORα, NR1D1, PPARα, JNK, IKKβ, NF-κB, AP-1, prediabetes, corticosterone, intestinal homeostasis
MeSH terms
Animals, Corticosterone, Ileum, Intestinal Mucosa, Male, Mice, Inbred C57BL, NF-kappa B, Toll-Like Receptors, Mice, Metagenome, Nuclear Receptor Subfamily 1, Group D, Member 1, Nuclear Receptor Subfamily 1, Group F, Member 1

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