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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.
Afiliação
  • Tuganbaev T; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Mor U; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Bashiardes S; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Liwinski T; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel; 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Nobs SP; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Leshem A; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • Dori-Bachash M; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Thaiss CA; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Pinker EY; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Ratiner K; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Adlung L; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Federici S; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Kleimeyer C; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Moresi C; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Yamada T; Division of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
  • Cohen Y; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Zhang X; Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
  • Massalha H; Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Massasa E; Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Kuperman Y; Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Koni PA; Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.
  • Harmelin A; Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Gao N; Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
  • Itzkovitz S; Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Honda K; RIKEN Center for Integrative Medical Sciences (IMS), Tsurumi, Yokohama, Kanagawa 230-0045, Japan; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
  • Shapiro H; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: hagit.shapiro@weizmann.ac.il.
  • Elinav E; Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel; Division of Cancer-Microbiome Research, DKFZ, Heidelberg 69120, Germany. Electronic address: eran.elinav@weizmann.ac.il.
Cell ; 182(6): 1441-1459.e21, 2020 09 17.
Article em En | MEDLINE | ID: mdl-32888430
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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Doença de Crohn / Antígenos de Histocompatibilidade Classe II / Células Epiteliais / Transcriptoma / Microbioma Gastrointestinal / Intestino Delgado Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Israel

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Doença de Crohn / Antígenos de Histocompatibilidade Classe II / Células Epiteliais / Transcriptoma / Microbioma Gastrointestinal / Intestino Delgado Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Israel