{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:04:39Z","timestamp":1789452279702,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sleep fragmentation is common in inflammatory bowel disease, but whether different fragmentation frequencies are associated with distinct biological responses during colitis remains unclear. This study examined endpoint-specific responses to low- and high-frequency sleep fragmentation in DSS-induced colitis in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6 mice were assigned to Control, DSS, DSS with low-frequency sleep fragmentation (DSS+LSF), DSS with high-frequency sleep fragmentation (DSS+HSF), or high-frequency sleep fragmentation alone (HSF). Colitis was induced with 2% DSS for 7 days. Sleep fragmentation was applied for 12 h\/day during the light phase at 60 sweeps\/h for LSF or 240 sweeps\/h for HSF. Clinical indices, histology, epithelial barrier-associated proteins, inflammatory and stress-related markers, colonic CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell subsets, fecal microbiota composition, and fecal SCFAs were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinical and macroscopic indices varied across experimental groups, but corrected comparisons among DSS-treated groups were not significant. Plasma corticosterone was increased in both DSS+LSF and DSS+HSF, whereas MPO was higher in DSS+LSF than in DSS+HSF. Colonic Th2 proportions were higher in DSS+HSF than in DSS and DSS+LSF. Other histological, barrier-associated, inflammatory, and metabolic findings were primarily descriptive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Low- and high-frequency sleep fragmentation were associated with distinct, endpoint-specific response profiles during DSS-induced colitis rather than a simple linear increase in disease severity. These findings support frequency-associated, domain-specific responses and warrant further longitudinal and mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1885856","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:36:25Z","timestamp":1789450585000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sleep fragmentation frequency is associated with distinct immune, microbial, and barrier-related profiles in DSS-induced colitis in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Ming-Shih","family":"Tu","sequence":"first","affiliation":[{"name":"Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-An","family":"Fan","sequence":"additional","affiliation":[{"name":"Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Chin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Department of Anatomic Pathology, Linkou Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jung","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Sleep Center, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]},{"name":"Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Pang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Sleep Center, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]},{"name":"Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Sleep Center, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]},{"name":"Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Lung","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Sleep Center, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]},{"name":"Division of Acupuncture and Moxibustion, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang-Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Linkou Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]},{"name":"School of Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Johns Hopkins Bloomberg School of Public Health","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng-Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Traditional Chinese Medicine, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"School of Traditional Chinese Medicine, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"name":"Sleep Center, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]},{"name":"Division of Acupuncture and Moxibustion, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804647","article-title":"Inflammatory bowel disease","volume":"361","author":"Abraham","year":"2009","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/sleepadvances\/zpac025","article-title":"A systematic review and meta-analysis of the prevalence of poor sleep in inflammatory bowel disease","volume":"3","author":"Barnes","year":"2022","journal-title":"Sleep Adv"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3580-5","article-title":"High C-Reactive Protein is associated with poor sleep quality independent of nocturnal symptoms in patients with inflammatory bowel disease","volume":"60","author":"Wilson","year":"2015","journal-title":"Dig Dis Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.20524\/aog.2020.0529","article-title":"Polysomnography shows sleep fragmentation in patients with inactive inflammatory bowel disease","volume":"33","author":"Beilman","year":"2020","journal-title":"Ann Gastroenterol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.01.021","article-title":"Sleep disturbance and risk of active disease in patients with Crohn's disease and ulcerative colitis","volume":"11","author":"Ananthakrishnan","year":"2013","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.04.021","article-title":"Sleep duration affects risk for ulcerative colitis: a prospective cohort study","volume":"12","author":"Ananthakrishnan","year":"2014","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1237-9","article-title":"Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases","volume":"569","author":"Lloyd-Price","year":"2019","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-304833","article-title":"A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis","volume":"63","author":"Machiels","year":"2014","journal-title":"Gut"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature12721","article-title":"Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00535-016-1242-9","article-title":"Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases","volume":"52","author":"Sun","year":"2017","journal-title":"J Gastroenterol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00277","article-title":"Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases","volume":"10","author":"Parada Venegas","year":"2019","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2009.06.022","article-title":"The tight junction in inflammatory disease: communication breakdown","volume":"9","author":"Edelblum","year":"2009","journal-title":"Curr Opin Pharmacol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izac219","article-title":"Colonic epithelial circadian disruption worsens dextran sulfate sodium-induced colitis","volume":"29","author":"Jochum","year":"2023","journal-title":"Inflamm. Bowel Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2017.08.014","article-title":"Sleep and circadian hygiene and inflammatory bowel disease","volume":"46","author":"Swanson","year":"2017","journal-title":"Gastroenterol Clin North Am"},{"key":"B15","article-title":"Obstructive sleep apnoea: definitions, epidemiology & natural history","volume":"131","author":"Lam","year":"2010","journal-title":"Indian J Med Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.sleep.2021.08.003","article-title":"Relationship between sleep disorders and gut dysbiosis: what affects what","volume":"87","author":"Neroni","year":"2021","journal-title":"Sleep Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00039.2020","article-title":"Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats","volume":"52","author":"Maki","year":"2020","journal-title":"Physiol Genomics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.sleep.2008.12.009","article-title":"Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis","volume":"10","author":"Tang","year":"2009","journal-title":"Sleep Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"718617","DOI":"10.1155\/2012\/718617","article-title":"Dextran sodium sulphate colitis mouse model: traps and tricks","volume":"2012","author":"Per\u0161e","year":"2012","journal-title":"J Biomed Biotechnol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"962","DOI":"10.3390\/biology11070962","article-title":"Alterations in gut microbiota and upregulations of VPAC2 and intestinal tight junctions correlate with anti-inflammatory effects of electroacupuncture in colitis mice with sleep fragmentation","volume":"11","author":"Liu","year":"2022","journal-title":"Biol (Basel)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s10787-014-0227-7","article-title":"Thermal spring water drinking attenuates dextran-sulfate-sodium-induced colitis in mice","volume":"23","author":"Pozsgai","year":"2015","journal-title":"Inflammopharmacology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.04.020","article-title":"Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection","volume":"131","author":"Van der Sluis","year":"2006","journal-title":"Gastroenterology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/jci118878","article-title":"Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27\/human beta2 microglobulin transgenic rats","volume":"98","author":"Rath","year":"1996","journal-title":"J Clin Invest"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.315","article-title":"Isolation and subsequent analysis of murine lamina propria mononuclear cells from colonic tissue","volume":"2","author":"Weigmann","year":"2007","journal-title":"Nat Protoc"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat Methods"},{"key":"B27","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s40168-018-0470-z","article-title":"Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2's q2-feature-classifier plugin","volume":"6","author":"Bokulich","year":"2018","journal-title":"Microbiome"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol Biol Evol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009490","article-title":"FastTree 2--approximately maximum-likelihood trees for large alignments","volume":"5","author":"Price","year":"2010","journal-title":"PLoS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/aem.01996-06","article-title":"Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities","volume":"73","author":"Lozupone","year":"2007","journal-title":"Appl Environ Microbiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/aem.71.12.8228-8235.2005","article-title":"UniFrac: a new phylogenetic method for comparing microbial communities","volume":"71","author":"Lozupone","year":"2005","journal-title":"Appl Environ Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2658","article-title":"Differential abundance analysis for microbial marker-gene surveys","volume":"10","author":"Paulson","year":"2013","journal-title":"Nat Methods"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0288889","article-title":"Temporal dynamics of pro-inflammatory cytokines and serum corticosterone following acute sleep fragmentation in male mice","volume":"18","author":"Nguyen","year":"2023","journal-title":"PLoS One"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00049.2015","article-title":"Acute sleep fragmentation induces tissue-specific changes in cytokine gene expression and increases serum corticosterone concentration","volume":"308","author":"Dumaine","year":"2015","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/nyas.14798","article-title":"Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival","volume":"1514","author":"Kuo","year":"2022","journal-title":"Ann N Y Acad Sci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0126-x","article-title":"Mechanisms regulating intestinal barrier integrity and its pathological implications","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp Mol Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.ajpath.2023.10.004","article-title":"Sleep deprivation impairs intestinal mucosal barrier by activating endoplasmic reticulum stress in goblet cells","volume":"194","author":"Li","year":"2024","journal-title":"Am J Pathol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12574","article-title":"Role of melatonin in sleep deprivation-induced intestinal barrier dysfunction in mice","volume":"67","author":"Gao","year":"2019","journal-title":"J Pineal Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/srep35405","article-title":"Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice","volume":"6","author":"Poroyko","year":"2016","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229001","article-title":"Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome","volume":"15","author":"Bowers","year":"2020","journal-title":"PLoS One"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.17539","article-title":"Effect of glucocorticoid blockade on inflammatory responses to acute sleep fragmentation in male mice","volume":"12","author":"Hasan","year":"2024","journal-title":"PeerJ"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00358.2019","article-title":"Chemical sympathectomy reduces peripheral inflammatory responses to acute and chronic sleep fragmentation","volume":"318","author":"Mishra","year":"2020","journal-title":"Am J Physiol Regul Integr Comp Physiol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1885856\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:36:26Z","timestamp":1789450586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1885856\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2026.1885856"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1885856","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"1885856"}}