{"doi":"10.1093/ibd/izac219","title":"Colonic Epithelial Circadian Disruption Worsens Dextran Sulfate Sodium–Induced Colitis","abstract":"BACKGROUND: Disruption of central circadian rhythms likely mediated by changes in microbiota and a decrease in gut-derived metabolites like short chain fatty acids (SCFAs) negatively impacts colonic barrier homeostasis. We aimed to explore the effects of isolated peripheral colonic circadian disruption on the colonic barrier in a mouse model of colitis and explore the mechanisms, including intestinal microbiota community structure and function. METHODS: Colon epithelial cell circadian rhythms were conditionally genetically disrupted in mice: TS4Cre-BMAL1lox (cBMAL1KO) with TS4Cre as control animals. Colitis was induced through 5 days of 2% dextran sulfate sodium (DSS). Disease activity index and intestinal barrier were assessed, as were fecal microbiota and metabolites. RESULTS: Colitis symptoms were worse in mice with peripheral circadian disruption (cBMAL1KO). Specifically, the disease activity index and intestinal permeability were significantly higher in circadian-disrupted mice compared with control animals (TS4Cre) (P < .05). The worsening of colitis appears to be mediated, in part, through JAK (Janus kinase)-mediated STAT3 (signal transducer and activator of transcription 3), which was significantly elevated in circadian-disrupted (cBMAL1KO) mice treated with DSS (P < .05). Circadian-disrupted (cBMAL1KO) mice also had decreased SCFA metabolite concentrations and decreased relative abundances of SCFA-producing bacteria in their stool when compared with control animals (TS4Cre). CONCLUSIONS: Disruption of intestinal circadian rhythms in colonic epithelial cells promoted more severe colitis, increased inflammatory mediators (STAT3 [signal transducer and activator of transcription 3]), and decreased gut microbiota-derived SCFAs compared with DSS alone. Further investigation elucidating the molecular mechanisms behind these findings could provide novel circadian directed targets and strategies in the treatment of inflammatory bowel disease.","journal":"Inflammatory Bowel Diseases","year":2022,"id":244944,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331442,"name":"Phillip A. Engen","orcid":"0000-0002-5276-5174","position":1,"is_corresponding":false},{"id":332950,"name":"Maliha Shaikh","orcid":null,"position":2,"is_corresponding":false},{"id":331444,"name":"Ankur Naqib","orcid":"0000-0003-0832-5646","position":3,"is_corresponding":false},{"id":331443,"name":"Sherry Wilber","orcid":"0000-0002-2117-4670","position":4,"is_corresponding":false},{"id":724459,"name":"Shohreh Raeisi","orcid":"0000-0002-5641-1736","position":5,"is_corresponding":false},{"id":878891,"name":"Lijuan Zhang","orcid":"0000-0001-6857-3647","position":6,"is_corresponding":false},{"id":879343,"name":"Shiwen Song","orcid":null,"position":7,"is_corresponding":false},{"id":725146,"name":"Gabriella Sanzo","orcid":null,"position":8,"is_corresponding":false},{"id":878892,"name":"Vijit Chouhan","orcid":"0000-0002-4192-9196","position":9,"is_corresponding":false},{"id":354172,"name":"Frank C. Ko","orcid":"0000-0001-6532-2084","position":10,"is_corresponding":false},{"id":878893,"name":"Zoë Post","orcid":"0000-0002-3397-507X","position":11,"is_corresponding":false},{"id":878894,"name":"Laura Tran","orcid":"0000-0002-4428-053X","position":12,"is_corresponding":false},{"id":879344,"name":"Vivian Ramirez","orcid":null,"position":13,"is_corresponding":false},{"id":284238,"name":"Stefan J. Green","orcid":"0000-0003-2781-359X","position":14,"is_corresponding":false},{"id":409816,"name":"Khashayarsha Khazaie","orcid":"0000-0002-7884-1817","position":15,"is_corresponding":false},{"id":878895,"name":"Dana M. Hayden","orcid":"0000-0002-0358-529X","position":16,"is_corresponding":false},{"id":878896,"name":"Mark J. F. Brown","orcid":"0000-0002-8887-3628","position":17,"is_corresponding":false},{"id":659077,"name":"Robin M. Voigt","orcid":"0000-0002-8010-0786","position":18,"is_corresponding":false},{"id":551651,"name":"Christopher B. 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