{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T04:26:46Z","timestamp":1786854406636,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571143"],"award-info":[{"award-number":["82571143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82571143"],"award-info":[{"award-number":["82571143"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Key Clinical Program on Orthodontics","award":["2023ZZ02009"],"award-info":[{"award-number":["2023ZZ02009"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFC3605600"],"award-info":[{"award-number":["2023YFC3605600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic metabolic disorders. However, the mechanisms underlying CIH-induced intestinal dysfunction remain unclear. In this study, we investigated the effects of CIH on intestinal barrier integrity, gut microbiota, and host metabolism using a multi-omics approach. Male C57BL\/6J mice were exposed to six weeks of CIH or normoxia. Colonic barrier integrity was assessed by histological and molecular analyses. Gut microbiota was profiled by full-length 16S rRNA gene sequencing. Untargeted metabolomics was performed on fecal and serum samples, followed by integrated microbiome\u2013metabolome analysis. CIH markedly impaired colonic barrier integrity, as evidenced by disrupted crypt architecture, reduced goblet cell abundance, and decreased expression of ZO-1, Occludin, and Claudin-5. CIH also induced gut microbial dysbiosis, characterized by depletion of the beneficial mucin-associated bacterium Akkermansia muciniphila and enrichment of several anaerobic taxa. Metabolomic analysis revealed opposite alterations of PC (20:2\/0:0) and LysoPE (20:5\/0:0) between feces and serum, whereas melatonin was consistently decreased in both compartments. Integrated multi-omics analysis further revealed close associations between microbial dysbiosis and metabolic remodeling. Collectively, these findings demonstrate that CIH disrupts intestinal homeostasis through coordinated alterations in barrier integrity, gut microbiota composition, and host metabolism, providing new insights into the intestinal mechanisms underlying OSA-associated systemic dysfunction.<\/jats:p>","DOI":"10.3390\/biom16081186","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:08:29Z","timestamp":1786694909000},"page":"1186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Intermittent Hypoxia Disrupts Intestinal Homeostasis Through Gut Microbiota Remodeling and Microbiota-Metabolite Interactions"],"prefix":"10.3390","volume":"16","author":[{"given":"Yuying","family":"He","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-537X","authenticated-orcid":false,"given":"Jun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0819-4992","authenticated-orcid":false,"given":"Mingrui","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3033-8873","authenticated-orcid":false,"given":"Yuehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 200001, China"},{"name":"Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41392-023-01496-3","article-title":"Pathophysiological Mechanisms and Therapeutic Approaches in Obstructive Sleep Apnea Syndrome","volume":"8","author":"Lv","year":"2023","journal-title":"Signal Transduct. 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