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Targeting the intestinal circadian clock by meal timing ameliorates gastrointestinal inflammation

Cellular & Molecular Immunology 2024年第8期21卷 842-855页

作者： Yunhui Niu Marjolein Heddes Baraa Altaha Michael Birkner karin kleigrewe Chen Meng Dirk Haller Silke Kiessling ZIEL-Institute for Food&Health Technical University of Munich85354FreisingGermany Chair of Nutrition and Immunology School of Life SciencesTechnical University of MunichGregor-Mendel-Str.285354FreisingGermany Bavarian Center for Biomolecular Mass Spectrometry Technical University of MunichGregor-Mendel-Str.485354FreisingGermany Faculty of Health and Medical Sciences University of SurreyStag Hill CampusGU27XPGuildfordUK

The expression of clock genes has been observed to be impaired in biopsies from patients with inflammatory bowel disease(IBD).Disruption of circadian rhythms,which occurs in shift workers,has been linked to an increased risk of gastrointestinal diseases,including *** peripheral circadian clock in intestinal epithelial cells(IECs)was previously shown to balance gastrointestinal homeostasis by regulating the ***,we demonstrated that the intestinal clock is disrupted in an IBD-relevant mouse model(IL-10−/−).A lack of the intestinal clock gene(Bmal1)in intestinal epithelial cells(IECs)in a chemically and a novel genetically induced colitis model(DSS,Bmal1IEC−/−xIL-10−/−)promoted colitis and dramatically reduced survival ***-free Bmal1IEC−/−mice colonized with disease-associated microbiota from IL-10−/−mice exhibited increased inflammatory responses,highlighting the importance of the local intestinal clock for microbiota-induced IBD *** the intestinal clock directly by timed restricted feeding(RF)in IL-10−/−mice restored intestinal clock functions,including immune cell recruitment and microbial rhythmicity;improved inflammatory responses;dramatically enhanced survival rates and rescued the histopathological *** contrast,RF failed to improve IBD symptoms in Bmal1IEC−/−xIL-10−/−mice,demonstrating the significance of the intestinal clock in determining the beneficial effect of ***,we provide evidence that intestinal clock dysfunction triggers host immune imbalance and promotes the development and progression of IBD-like *** intestinal clock function by RF modulates the pathogenesis of IBD and thus could become a novel strategy to ameliorate symptoms in IBD patients.

关键词： Intestinal circadian clock Gastrointestinal inflammation IBD Restricted feeding Microbiota

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