Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis
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Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis. / Tuganbaev, Timur; Mor, Uria; Bashiardes, Stavros; Liwinski, Timur; Nobs, Samuel Philip; Leshem, Avner; Dori-Bachash, Mally; Thaiss, Christoph A; Pinker, Elisha Y; Ratiner, Karina; Adlung, Lorenz; Federici, Sara; Kleimeyer, Christian; Moresi, Claudia; Yamada, Takahiro; Cohen, Yotam; Zhang, Xiao; Massalha, Hassan; Massasa, Efi; Kuperman, Yael; Koni, Pandelakis A; Harmelin, Alon; Gao, Nan; Itzkovitz, Shalev; Honda, Kenya; Shapiro, Hagit; Elinav, Eran.
in: CELL, Jahrgang 182, Nr. 6, 17.09.2020, S. 1441-1459.e21.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis
AU - Tuganbaev, Timur
AU - Mor, Uria
AU - Bashiardes, Stavros
AU - Liwinski, Timur
AU - Nobs, Samuel Philip
AU - Leshem, Avner
AU - Dori-Bachash, Mally
AU - Thaiss, Christoph A
AU - Pinker, Elisha Y
AU - Ratiner, Karina
AU - Adlung, Lorenz
AU - Federici, Sara
AU - Kleimeyer, Christian
AU - Moresi, Claudia
AU - Yamada, Takahiro
AU - Cohen, Yotam
AU - Zhang, Xiao
AU - Massalha, Hassan
AU - Massasa, Efi
AU - Kuperman, Yael
AU - Koni, Pandelakis A
AU - Harmelin, Alon
AU - Gao, Nan
AU - Itzkovitz, Shalev
AU - Honda, Kenya
AU - Shapiro, Hagit
AU - Elinav, Eran
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020/9/17
Y1 - 2020/9/17
N2 - Throughout a 24-h period, the small intestine (SI) is exposed to diurnally varying food- and microbiome-derived antigenic burdens but maintains a strict immune homeostasis, which when perturbed in genetically susceptible individuals, may lead to Crohn disease. Herein, we demonstrate that dietary content and rhythmicity regulate the diurnally shifting SI epithelial cell (SIEC) transcriptional landscape through modulation of the SI microbiome. We exemplify this concept with SIEC major histocompatibility complex (MHC) class II, which is diurnally modulated by distinct mucosal-adherent SI commensals, while supporting downstream diurnal activity of intra-epithelial IL-10+ lymphocytes regulating the SI barrier function. Disruption of this diurnally regulated diet-microbiome-MHC class II-IL-10-epithelial barrier axis by circadian clock disarrangement, alterations in feeding time or content, or epithelial-specific MHC class II depletion leads to an extensive microbial product influx, driving Crohn-like enteritis. Collectively, we highlight nutritional features that modulate SI microbiome, immunity, and barrier function and identify dietary, epithelial, and immune checkpoints along this axis to be potentially exploitable in future Crohn disease interventions.
AB - Throughout a 24-h period, the small intestine (SI) is exposed to diurnally varying food- and microbiome-derived antigenic burdens but maintains a strict immune homeostasis, which when perturbed in genetically susceptible individuals, may lead to Crohn disease. Herein, we demonstrate that dietary content and rhythmicity regulate the diurnally shifting SI epithelial cell (SIEC) transcriptional landscape through modulation of the SI microbiome. We exemplify this concept with SIEC major histocompatibility complex (MHC) class II, which is diurnally modulated by distinct mucosal-adherent SI commensals, while supporting downstream diurnal activity of intra-epithelial IL-10+ lymphocytes regulating the SI barrier function. Disruption of this diurnally regulated diet-microbiome-MHC class II-IL-10-epithelial barrier axis by circadian clock disarrangement, alterations in feeding time or content, or epithelial-specific MHC class II depletion leads to an extensive microbial product influx, driving Crohn-like enteritis. Collectively, we highlight nutritional features that modulate SI microbiome, immunity, and barrier function and identify dietary, epithelial, and immune checkpoints along this axis to be potentially exploitable in future Crohn disease interventions.
KW - Animals
KW - Anti-Bacterial Agents/pharmacology
KW - Circadian Clocks/physiology
KW - Crohn Disease/immunology
KW - Diet
KW - Epithelial Cells/cytology
KW - Flow Cytometry
KW - Gastrointestinal Microbiome/drug effects
KW - Gene Expression Profiling
KW - Histocompatibility Antigens Class II/genetics
KW - Homeostasis
KW - In Situ Hybridization, Fluorescence
KW - Interleukin-10/metabolism
KW - Intestine, Small/immunology
KW - Lymphocytes
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Periodicity
KW - T-Lymphocytes/immunology
KW - Transcriptome/genetics
U2 - 10.1016/j.cell.2020.08.027
DO - 10.1016/j.cell.2020.08.027
M3 - SCORING: Journal article
C2 - 32888430
VL - 182
SP - 1441-1459.e21
JO - CELL
JF - CELL
SN - 0092-8674
IS - 6
ER -