Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis
- PMID: 32888430
- DOI: 10.1016/j.cell.2020.08.027
Diet Diurnally Regulates Small Intestinal Microbiome-Epithelial-Immune Homeostasis and Enteritis
Abstract
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.
Keywords: Crohn disease; HFD; IBD; IL-10; MHC class II; SFB; circadian clock; epithelial cell; high-fat diet; inflammatory bowel disease; interleukin-10; major histocompatibility complex; microbiome; segmented filamentous bacteria; small intestine.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Interests E.E. is a consultant to DayTwo and BiomX. None of the topics related to this work involve these or other commercial entities. None of the other authors have any financial or non-financial competing interest.
Comment in
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Time matters: The circadian rhythm in intestinal homeostasis and food allergy.Allergy. 2021 Sep;76(9):2931-2933. doi: 10.1111/all.14887. Epub 2021 May 25. Allergy. 2021. PMID: 33914931 No abstract available.
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