{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:52:31Z","timestamp":1774421551010,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"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. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is characterized by chronic colonic mucosal inflammation, with its pathogenesis involving multidimensional interactions and limitations in clinical treatment. Dietary restriction (DR) is a commonly used approach for UC patients to alleviate symptoms, and exploring the role of DR-related genes in UC could provide new directions for the development of precision therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bioinformatics analysis was performed on UC-related datasets (GSE75214, GSE73661) obtained from the GEO database. Candidate genes were acquired by intersecting differentially expressed genes (DEGs) with dietary restriction-related genes (DRRGs). Subsequently, key genes were identified via machine learning algorithms and ROC curve analysis. A deep neural network (DNN) model and a diagnostic nomogram were constructed. In addition, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), immune infiltration analysis, and single-cell RNA sequencing (scRNA-seq) analysis were conducted. Finally, the expression of key genes was validated through experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CPT1A, ANGPTL4, and CLDN1 were identified as the key genes. The deep neural network (DNN) model achieved area under the curve (AUC) values of 0.914 and 0.933 in the two datasets, respectively; the diagnostic nomogram exhibited high predictive performance (AUC &amp;gt; 0.7), and decision curve analysis (DCA) revealed its potential clinical net benefit. Enrichment analyses demonstrated that the key genes were significantly enriched in dietary restriction (DR)-related pathways, including cytokine-receptor interaction, the IL2-STAT5 signaling pathway, and fatty acid metabolism. Thirty-two activated pathways and five inhibited pathways were detected in UC patients (e.g., the oxidative phosphorylation pathway was suppressed). Immune infiltration analysis identified 27 differentially infiltrating immune cell types. CLDN1 was localized to epithelial cells, ANGPTL4 to fibroblasts, and CPT1A to endothelial cells. Macrophages were identified as a signaling hub in UC, showing intensified crosstalk with stromal and vascular cells via pathways such as ACKR1. Experimental validation confirmed that ANGPTL4 and CLDN1 were highly expressed in UC, whereas CPT1A was lowly expressed, a pattern consistent with the expression trends observed in public database analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results indicated that CPT1A, ANGPTL4, and CLDN1 are involved in the pathological regulation of UC by DR through modulating the metabolism-immune-barrier axis, providing novel biomarkers and potential intervention targets for the clinical diagnosis and targeted therapy of UC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1786138","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:35:19Z","timestamp":1774416919000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Revealing key genes and molecular mechanisms associated with dietary restriction in ulcerative colitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yingying","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qijin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9751","DOI":"10.3390\/ijms25219751","article-title":"Key disease-related genes and immune cell infiltration landscape in inflammatory bowel disease: a bioinformatics investigation","volume":"25","author":"Alghamdi","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5242","DOI":"10.1080\/10408398.2022.2153794","article-title":"Dietary restriction in senolysis and prevention and treatment of disease","volume":"64","author":"Aminzadeh-Gohari","year":"2024","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1093\/ecco-jcc\/jjx136","article-title":"Fibre intake and the development of inflammatory bowel disease: a European prospective multi-centre cohort study (EPIC-IBD)","volume":"12","author":"Andersen","year":"2018","journal-title":"J. Crohn\u2019s Colitis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1136\/gutjnl-2016-312293","article-title":"Effect of vedolizumab (anti-\u03b14\u03b27-integrin) therapy on histological healing and mucosal gene expression in patients with UC","volume":"67","author":"Arijs","year":"2018","journal-title":"Gut"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.3390\/nu13041067","article-title":"Food and food groups in inflammatory bowel disease (IBD): the design of the Groningen anti-inflammatory diet (GrAID)","volume":"13","author":"Campmans-Kuijpers","year":"2021","journal-title":"Nutrients"},{"key":"B6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1471-2105-12-35","article-title":"VennDiagram: a package for the generation of highly-customizable venn and euler diagrams in R","volume":"12","author":"Chen","year":"2011","journal-title":"BMC Bioinforma."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.3390\/biomedicines13051035","article-title":"Prognostic significance of CLDN1, INHBA, and CXCL12 in Colon adenocarcinoma: a multi-omics and single-cell approach","volume":"13","author":"Cheon","year":"2025","journal-title":"Biomedicines"},{"key":"B8","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1093\/ecco-jcc\/jjw142","article-title":"Reduced mucosa-associated butyricicoccus activity in patients with ulcerative colitis correlates with aberrant claudin-1 expression","volume":"11","author":"Devriese","year":"2017","journal-title":"J. Crohn\u2019s Colitis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/s41586-024-08026-3","article-title":"Dietary restriction impacts health and lifespan of genetically diverse mice","volume":"634","author":"Di Francesco","year":"2024","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.3390\/nu16101504","article-title":"Effects of mediterranean diet, curcumin, and resveratrol on mild-to-moderate active ulcerative colitis: a multicenter randomized clinical trial","volume":"16","author":"Erol Do\u011fan","year":"2024","journal-title":"Nutrients"},{"key":"B11","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41580-021-00411-4","article-title":"Molecular mechanisms of dietary restriction promoting health and longevity","volume":"23","author":"Green","year":"2022","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1001\/jama.2023.15389","article-title":"Ulcerative colitis in adults: a review","volume":"330","author":"Gros","year":"2023","journal-title":"JAMA"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1093\/bioinformatics\/btab806","article-title":"Make interactive complex heatmaps in R","volume":"38","author":"Gu","year":"2022","journal-title":"Bioinformatics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3844","DOI":"10.1093\/bioinformatics\/btac409","article-title":"Ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2","volume":"38","author":"Gustavsson","year":"2022","journal-title":"Bioinformatics"},{"key":"B15","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 Bioinforma."},{"key":"B16","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s10545-010-9061-2","article-title":"A general introduction to the biochemistry of mitochondrial fatty acid \u03b2-oxidation","volume":"33","author":"Houten","year":"2010","journal-title":"J. Inherit. Metabolic Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/s41586-025-08940-0","article-title":"Global evolution of inflammatory bowel disease across epidemiologic stages","volume":"642","author":"Hracs","year":"2025","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","first-page":"890","DOI":"10.3390\/nu13030890","article-title":"Therapeutic implications of diet in inflammatory bowel disease and related immune-mediated inflammatory diseases","volume":"13","author":"Jiang","year":"2021","journal-title":"Nutrients"},{"key":"B19","doi-asserted-by":"publisher","first-page":"925695","DOI":"10.3389\/fimmu.2022.925695","article-title":"Identification of critical biomarkers and immune infiltration in rheumatoid arthritis based on WGCNA and LASSO algorithm","volume":"13","author":"Jiang","year":"2022","journal-title":"Front. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3248","DOI":"10.1097\/JS9.0000000000002335","article-title":"Higher Life's essential 8 score is associated with reduced risk of related surgery and all-cause mortality among 3232 individuals with inflammatory bowel disease in a longitudinal cohort study","volume":"111","author":"Jing","year":"2025","journal-title":"Int. J. Surg."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.cgh.2024.01.013","article-title":"Coconut water induces clinical remission in mild to moderate ulcerative colitis: double-blind placebo-controlled trial","volume":"22","author":"Kedia","year":"2024","journal-title":"Clin. Gastroenterology Hepatology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1388-1981(00)00044-5","article-title":"Fatty acid import into mitochondria","volume":"1486","author":"Kerner","year":"2000","journal-title":"Biochimica Biophysica Acta (BBA) - Mol. Cell. Biol. Lipids"},{"key":"B23","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41572-020-0205-x","article-title":"Ulcerative colitis","volume":"6","author":"Kobayashi","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B24","doi-asserted-by":"publisher","first-page":"564","DOI":"10.3238\/arztebl.2020.0564","article-title":"Ulcerative colitis-diagnostic and therapeutic algorithms","volume":"117","author":"Kucharzik","year":"2020","journal-title":"Dtsch. \u00c4rzteblatt Int."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J. Stat. Softw."},{"key":"B26","doi-asserted-by":"publisher","first-page":"117553","DOI":"10.1016\/j.lfs.2020.117553","article-title":"EZH2 inhibition promotes ANGPTL4\/CREB1 to suppress the progression of ulcerative colitis","volume":"250","author":"Li","year":"2020","journal-title":"Life Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"447","DOI":"10.3390\/jpm13030447","article-title":"Construction of osteosarcoma diagnosis model by random forest and artificial neural network","volume":"13","author":"Li","year":"2023","journal-title":"J. Personalized Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.crohns.2012.07.018","article-title":"One more time\u2019 5-ASA retrial after a glucocorticosteroid induced remission in moderate to severe ulcerative colitis: a prospective community practice experience","volume":"7","author":"Lipka","year":"2013","journal-title":"J. Crohn\u2019s Colitis"},{"key":"B29","doi-asserted-by":"publisher","first-page":"14063","DOI":"10.1038\/ncomms14063","article-title":"Caloric restriction improves health and survival of rhesus monkeys","volume":"8","author":"Mattison","year":"2017","journal-title":"Nat. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"111741","DOI":"10.1016\/j.mad.2022.111741","article-title":"Dietary restriction and aging: recent evolutionary perspectives","volume":"208","author":"McAuley","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1802441","DOI":"10.1183\/13993003.02441-2018","article-title":"Proliferating SPP1\/MERTK-expressing macrophages in idiopathic pulmonary fibrosis","volume":"54","author":"Morse","year":"2019","journal-title":"Eur. Respir. J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1016\/S0140-6736(12)60150-0","article-title":"Ulcerat colitis","volume":"380","author":"Ord\u00e1s","year":"2012","journal-title":"Lancet"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1038\/s42255-025-01415-6","article-title":"Dietary restriction reprograms CD8+ T cell fate to enhance anti-tumour immunity and immunotherapy responses","volume":"7","author":"Oswald","year":"2025","journal-title":"Nat. Metab."},{"key":"B35","doi-asserted-by":"publisher","first-page":"S189","DOI":"10.1016\/S1525-0016(16)33204-7","article-title":"477. ANGPTL4 limits the extent of colonic inflammation","volume":"24","author":"Phua","year":"2016","journal-title":"Mol. Ther."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"653","DOI":"10.7150\/jca.66450","article-title":"Decreased E2F2 expression correlates with poor prognosis and immune infiltrates in patients with colorectal cancer","volume":"13","author":"Shang","year":"2022","journal-title":"J. Cancer"},{"key":"B38","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1093\/bioinformatics\/btq675","article-title":"Cytoscape 2.8: new features for data integration and network visualization","volume":"27","author":"Smoot","year":"2011","journal-title":"Bioinformatics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105078","DOI":"10.1016\/j.ebiom.2024.105078","article-title":"An integrative pan-cancer analysis of the molecular characteristics of dietary restriction in tumour microenvironment","volume":"102","author":"Song","year":"2024","journal-title":"EBioMedicine"},{"key":"B40","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.bbrc.2020.08.081","article-title":"Upregulation of hsa-miR-31-3p induced by ultraviolet affects keratinocytes permeability barrier by targeting CLDN1","volume":"532","author":"Tu","year":"2020","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1097\/MIB.0000000000001246","article-title":"Genetic and transcriptomic bases of intestinal epithelial barrier dysfunction in inflammatory bowel disease","volume":"23","author":"Vancamelbeke","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1002\/eji.201747176","article-title":"Proteome analysis of human CD56neg NK cells reveals a homogeneous phenotype surprisingly similar to CD56dim NK cells","volume":"48","author":"Voigt","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1149686","DOI":"10.3389\/fimmu.2023.1149686","article-title":"A comprehensive analysis of biomarkers associated with synovitis and chondrocyte apoptosis in osteoarthritis","volume":"14","author":"Yang","year":"2023","journal-title":"Front. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"jjaf036","DOI":"10.1093\/ecco-jcc\/jjaf036","article-title":"Higher dietary glycemic index, but not glycemic load, is associated with increased risk of ulcerative colitis: a prospective cohort study","volume":"19","author":"Ye","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e13265","DOI":"10.1002\/ijop.13265","article-title":"Getting started with the graded response model: an introduction and tutorial in R","volume":"60","author":"Zein","year":"2025","journal-title":"Int. J. Psychol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/1471-2105-14-244","article-title":"RCircos: an R package for circos 2D track plots","volume":"14","author":"Zhang","year":"2013","journal-title":"BMC Bioinforma."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s00011-023-01747-7","article-title":"Dual role of ANGPTL4 in inflammation","volume":"72","author":"Zuo","year":"2023","journal-title":"Inflamm. Res."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1786138\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:35:21Z","timestamp":1774416921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1786138\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":48,"alternative-id":["10.3389\/fmolb.2026.1786138"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2026.1786138","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"article-number":"1786138"}}