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

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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

DOI 10.1016/j.cell.2013.04.020

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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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Peer Review #3 of "Circadian disruption and divergent microbiota acquisition under extended photoperiod regimens in chicken (v0.1)"
(2019) · PeerJ · doi:10.7287/peerj.6592v0.1/reviews/3
Peer Review #4 of "Circadian disruption and divergent microbiota acquisition under extended photoperiod regimens in chicken (v0.2)"
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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
ORCID: Mukherji, Atish
Ye, Tao
Chambon, Pierre
Venue: Cell
Publisher: Elsevier BV
Published: 2013-05
Volume: 153
Issue: 4
Pages: 812-827
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2013.04.020
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 373 d)
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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Homeostasis in Intestinal Epithelium Is Orchestrated by the Circadian Clock and Microbiota Cues Transduced by TLRs

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