{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:30:33Z","timestamp":1792452633292,"version":"4.5.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"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>Lactylation modification serves as a critical link between metabolic reprogramming and epigenetic regulation, playing a significant role in the progression of both malignant tumors and inflammatory diseases. Nevertheless, its specific function in the pathogenesis of ulcerative colitis (UC) remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The hub genes associated with lactylation in UC were identified and validated by mining three UC-related datasets (GSE206285, GSE75214, and GSE87466) from the GEO database, and we created a lactylation-related prediction model for the diagnosis of UC. The lactylation levels of different immune cells were also investigated via single-cell (sc) RNA-sequencing data. Finally, the core genes of lactylation were validated\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four lactylation-related core genes (HIF1A, SLC25A12, SLC16A3, and PFKFB2) that are closely correlated with UC were identified by three machine learning methods, and the lactylation-related prediction model based on the four genes exhibited outstanding diagnostic performance for UC (AUC:0.976, 95% CI: 0.941\u20131.00). scRNA-sequencing analysis revealed that HSC, NK, and macrophage cells exhibited higher lactylation-related scores in UC compared to other immune cells. After Nala intervention, the expressions of the four core genes were significantly increased, while the expressions of the four genes were significantly decreased after treatment with 2-DG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By applying machine learning methods to analyze sequencing data, we identified core lactylation-related genes in UC and developed a diagnostic model with high predictive performance. Furthermore, based on scRNA-seq data, we investigated lactylation modifications across seven types of immune cells in UC patients, providing valuable insights into the interplay between lactylation and immune cells in UC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1717232","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:52:52Z","timestamp":1773211972000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A lactylation modification-related prediction model for the diagnosis of ulcerative colitis based on machine learning"],"prefix":"10.3389","volume":"17","author":[{"given":"Jian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, First Affiliated Hospital of Xi\u2019an JiaoTong University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Medicine, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaf094","article-title":"Gaps between European Crohn\u2019s Colitis Organisation quality standards of care and the real world on structure of IBD units across Europe: results from E-QUALITY survey","volume":"19","author":"Fiorino","year":"2025","journal-title":"J Crohns Colitis"},{"key":"B2","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":"B3","doi-asserted-by":"publisher","first-page":"101915","DOI":"10.3748\/wjg.v31.i22.101915","article-title":"Shared decision-making improves adherence to mesalamine in ulcerative colitis: A prospective, multicenter, non-interventional cohort study in Germany","volume":"31","author":"Kruis","year":"2025","journal-title":"World J Gastroenterol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70240","article-title":"Twenty-year trends in colectomy rates and advanced therapy prescribing in lothian, scotland","author":"Elford","year":"2025","journal-title":"Aliment Pharmacol Ther"},{"key":"B5","doi-asserted-by":"publisher","first-page":"109258","DOI":"10.1016\/j.envint.2025.109258","article-title":"Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage","volume":"195","author":"Tian","year":"2025","journal-title":"Environ Int"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00159.2022","article-title":"Lactylation: novel epigenetic regulatory and therapeutic opportunities","volume":"324","author":"Fan","year":"2023","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.09.006","article-title":"Lactylation in cancer: Current understanding and challenges","volume":"42","author":"Li","year":"2024","journal-title":"Cancer Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.11.017","article-title":"Dual activation of GCGR\/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells","volume":"15","author":"Liu","year":"2025","journal-title":"Acta Pharm Sin B"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1042","DOI":"10.1002\/iid3.1042","article-title":"Potential biomarker for diagnosis and therapy of sepsis: Lactylation","volume":"11","author":"Sun","year":"2023","journal-title":"Immun Inflammation Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1549724","article-title":"A novel lactylation-related gene signature to predict prognosis and treatment response in lung adenocarcinoma","volume":"15","author":"Zhang","year":"2025","journal-title":"Front. Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s12967-024-05092-z","article-title":"Immunological profile of lactylation-related genes in Crohn\u2019s disease: a comprehensive analysis based on bulk and single-cell RNA sequencing data","volume":"22","author":"Wu","year":"2024","journal-title":"J Transl Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"102468","DOI":"10.1016\/j.tice.2024.102468","article-title":"Gegen Qinlian decoction inhibited M1 macrophage polarization and ulcerative colitis progression through regulating histone lactylation","volume":"89","author":"Xu","year":"2024","journal-title":"Tissue Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2025.1589999","article-title":"Identification of neutrophil extracellular trap-related biomarkers in ulcerative colitis based on bioinformatics and machine learning","volume":"16","author":"Jiao","year":"2025","journal-title":"Front Genet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1103617","article-title":"Roles of macrophages on ulcerative colitis and colitis-associated colorectal cancer","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00841-9","article-title":"Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis","volume":"29","author":"Yang","year":"2022","journal-title":"Cell Death Differ"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1395786","article-title":"Lactate and lactylation in macrophage metabolic reprogramming: current progress and outstanding issues","volume":"15","author":"Xu","year":"2024","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e1614","DOI":"10.1002\/ctm2.1614","article-title":"Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription","volume":"14","author":"Zhang","year":"2024","journal-title":"Clin Transl Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0360OC","article-title":"Lung myofibroblasts promote macrophage profibrotic activity through lactate-induced histone lactylation","volume":"64","author":"Cui","year":"2021","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02178-8","article-title":"Targeting lactylation reinforces NK cell cytotoxicity within the tumor microenvironment","volume":"26","author":"Jin","year":"2025","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/d41586-025-00822-9","article-title":"Global cooperation is crucial for DeepSeek and broader AI research","volume":"639","author":"Liu","year":"2025","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-024-09544-y","article-title":"Integrating machine learning and multi-omics analysis to develop an asparagine metabolism immunity index for improving clinical outcome and drug sensitivity in lung adenocarcinoma","volume":"72","author":"Li","year":"2024","journal-title":"Immunol Res"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-34461-0_18","article-title":"Hypoxia compromises anti-cancer immune responses","volume":"1232","author":"Multhoff","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1187","article-title":"Targeting HIF-1 for cancer therapy","volume":"3","author":"Semenza","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046571","article-title":"Lactate activates HIF-1 in oxidative but not in Warburg-phenotype human tumor cells","volume":"7","author":"De Saedeleer","year":"2012","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/s41420-022-01052-y","article-title":"MTA1 aggravates experimental colitis in mice by promoting transcription factor HIF1A and up-regulating AQP4 expression","volume":"8","author":"Li","year":"2022","journal-title":"Cell Death Discov"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00736-8","article-title":"PFKFB2-mediated glycolysis promotes lactate-driven continual efferocytosis by macrophages","volume":"5","author":"Schilperoort","year":"2023","journal-title":"Nat Metab"},{"key":"B27","doi-asserted-by":"publisher","first-page":"150709","DOI":"10.1016\/j.bbrc.2024.150709","article-title":"Knockdown of SLC16A3 decreases extracellular lactate concentration in hepatocellular carcinoma, alleviates hypoxia and induces ferroptosis","volume":"733","author":"Shen","year":"2024","journal-title":"Biochem Biophys Res Commun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1717232\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:52:53Z","timestamp":1773211973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1717232\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":27,"alternative-id":["10.3389\/fimmu.2026.1717232"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1717232","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"article-number":"1717232"}}