{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:29:37Z","timestamp":1791487777423,"version":"4.3.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"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><jats:title>Background<\/jats:title><jats:p>Ulcerative colitis (UC) and periodontitis (PD) are chronic inflammatory diseases with increasing evidence of bidirectional communication through the oral\u2013gut axis. However, the immunological mechanisms underlying their co-occurrence remain largely unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a bidirectional Mendelian randomization (MR) analysis to evaluate potential causal relationships between UC and PD. Transcriptomic data from public repositories were integrated to identify shared differentially expressed genes. Immune-related genes were further screened using three machine learning approaches. Enrichment analysis and immune cell infiltration profiling were performed to explore underlying mechanisms. A rat model combining UC and PD was established to validate key findings <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MR analysis revealed a unidirectional causal effect of UC on PD. Among the intersected immune-related genes, CXCL6 was identified as a hub gene significantly upregulated in both UC and PD. It was associated with neutrophil infiltration and pathways related to chemokine signaling and mucosal barrier disruption. In a dual-disease rat model, CXCL6 expression was further elevated in colonic tissues compared to UC alone, aligning with aggravated epithelial damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study identifies a shared immune signature between UC and PD, highlighting CXCL6 as a pivotal mediator. These insights deepen understanding of oral\u2013gut mucosal interactions and inform future biomarker and mechanistic studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1668277","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:13:34Z","timestamp":1756268014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Shared immune-inflammatory mechanisms between ulcerative colitis and periodontitis: a multi-omics analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Hongjiao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peimin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Le Berre","year":"2023","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"15821","DOI":"10.1038\/s41598-023-43091-0","article-title":"Pyroptosis burden is associated with anti-TNF treatment outcome in inflammatory bowel disease: new insights from bioinformatics analysis","volume":"13","author":"Gao","year":"2023","journal-title":"Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2022.2047221","article-title":"Identification of gut microbiome and transcriptome changes in ulcerative colitis and pouchitis","volume":"57","author":"Gao","year":"2022","journal-title":"Scand J Gastroenterol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-332489","article-title":"Acute severe ulcerative colitis trials: the past, the present and the future","volume":"73","author":"Honap","year":"2024","journal-title":"Gut"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1013900","article-title":"Oral manifestations serve as potential signs of ulcerative colitis: A review","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.3390\/biomedicines12081839","article-title":"Extraintestinal manifestations in inflammatory bowel disease: from pathophysiology to treatment","volume":"12","author":"Faggiani","year":"2024","journal-title":"Biomedicines"},{"key":"B7","doi-asserted-by":"publisher","first-page":"5142","DOI":"10.3390\/ijms23095142","article-title":"Impact of oral microbiome in periodontal health and periodontitis: A critical review on prevention and treatment","volume":"23","author":"Di Stefano","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1002\/JPER.17-0486","article-title":"Active matrix metalloproteinase-8 and periodontal bacteria-interlink between periodontitis and inflammatory bowel disease","volume":"89","author":"Schmidt","year":"2018","journal-title":"J Periodontol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2019.8162","article-title":"History of inflammatory bowel disease and self-reported oral health: women\u2019s health initiative observational study","volume":"29","author":"Kato","year":"2020","journal-title":"J Womens Health (Larchmt)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v26.i37.5661","article-title":"Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study","volume":"26","author":"Kang","year":"2020","journal-title":"World J Gastroenterol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.3390\/ijerph15112602","article-title":"Increased risk of ulcerative colitis in patients with periodontal disease: A nationwide population-based cohort study","volume":"15","author":"Lin","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2016.06.024","article-title":"Inverse association between poor oral health and inflammatory bowel diseases","volume":"15","author":"Yin","year":"2017","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad188","article-title":"Causal association analysis of periodontitis and inflammatory bowel disease: A bidirectional mendelian randomization study","volume":"30","author":"Qing","year":"2024","journal-title":"Inflammation Bowel Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13782","article-title":"Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study","volume":"50","author":"Wang","year":"2023","journal-title":"J Clin Periodontol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izac241","article-title":"The oral-gut axis: periodontal diseases and gastrointestinal disorders","volume":"29","author":"Lam","year":"2023","journal-title":"Inflammation Bowel Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"112120","DOI":"10.1016\/j.celrep.2023.112120","article-title":"Periodontal disease is associated with increased gut colonization of pathogenic Haemophilus parainfluenzae in patients with Crohn\u2019s disease","volume":"42","author":"Sohn","year":"2023","journal-title":"Cell Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.22-0205","article-title":"Fusobacterium nucleatum aggravates ulcerative colitis through promoting gut microbiota dysbiosis and dysmetabolism","volume":"94","author":"Lin","year":"2023","journal-title":"J Periodontol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12816","article-title":"Ingestion of Porphyromonas gingivalis exacerbates colitis via intestinal epithelial barrier disruption in mice","volume":"56","author":"Tsuzuno","year":"2021","journal-title":"J Periodontal Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405634111","article-title":"Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut","volume":"111","author":"Morton","year":"2014","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad084","article-title":"Responsiveness to vedolizumab therapy in ulcerative colitis is associated with alterations in immune cell-cell communications","volume":"29","author":"Hsu","year":"2023","journal-title":"Inflammation Bowel Dis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"B22","doi-asserted-by":"publisher","first-page":"18620","DOI":"10.1038\/s41598-023-45527-z","article-title":"Deciphering genetic causality between inflammatory bowel disease and periodontitis through bi-directional two-sample Mendelian randomization","volume":"13","author":"Yu","year":"2023","journal-title":"Sci Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1471-2105-14-125","article-title":"Random forest methodology for model-based recursive partitioning: the mobForest package for R","volume":"14","author":"Garge","year":"2013","journal-title":"BMC Bioinf"},{"key":"B25","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13148-019-0730-1","article-title":"Statistical predictions with glmnet","volume":"11","author":"Engebretsen","year":"2019","journal-title":"Clin Epigenet"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2017.00099","article-title":"Support vector machine analysis of functional magnetic resonance imaging of interoception does not reliably predict individual outcomes of cognitive behavioral therapy in panic disorder with agoraphobia","volume":"8","author":"Sundermann","year":"2017","journal-title":"Front Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000392","article-title":"Extraintestinal manifestations of inflammatory bowel disease","volume":"21","author":"Vavricka","year":"2015","journal-title":"Inflammation Bowel Dis"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae028","article-title":"Unravelling the oral-Gut axis: interconnection between periodontitis and inflammatory bowel disease, current challenges, and future perspective","volume":"18","author":"Tanwar","year":"2024","journal-title":"J Crohns Colitis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2018.09.004","article-title":"Healing of apical periodontitis in patients with inflammatory bowel diseases and under anti-tumor necrosis factor alpha therapy","volume":"44","author":"Cotti","year":"2018","journal-title":"J Endod"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.3390\/life11121409","article-title":"Changes in salivary parameters of oral immunity after biologic therapy for inflammatory bowel disease","volume":"11","author":"Nijakowski","year":"2021","journal-title":"Life (Basel)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/adj.12684","article-title":"Interaction of biologic therapy with apical periodontitis and periodontitis: a systematic review","volume":"64","author":"Peddis","year":"2019","journal-title":"Aust Dent J"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2174\/0929867327666200824112732","article-title":"Central regulatory role of cytokines in periodontitis and targeting options","volume":"28","author":"Plemmenos","year":"2021","journal-title":"Curr Med Chem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-023-01152-8","article-title":"CXCL6: A potential therapeutic target for inflammation and cancer","volume":"23","author":"Dai","year":"2023","journal-title":"Clin Exp Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1668277\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:13:36Z","timestamp":1756268016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1668277\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":34,"alternative-id":["10.3389\/fimmu.2025.1668277"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1668277","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,27]]},"article-number":"1668277"}}