{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:07Z","timestamp":1787034307422,"version":"build-2736575974"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diethyl phthalate (DEP) is a prevalent plasticizer with multiple toxic effects and high bioavailability in humans, especially children. Pediatric Crohn\u2019s disease (PCD) is a severe chronic intestinal inflammatory disorder with a rising incidence worldwide. To date, the potential associative relationship between DEP exposure and PCD pathogenesis remains inadequately clarified, lacking systematic transcriptomic and experimental exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, bioinformatics analysis was performed based on 682 PCD samples and 127 normal samples retrieved from multiple GEO datasets. A series of analytical strategies including differential expression analysis, weighted gene co-expression network analysis (WGCNA), compound target prediction, functional enrichment analysis, machine learning modeling, and molecular docking simulation were comprehensively utilized, followed by preliminary animal validation. All analyses in this study focused on exploring statistical correlation rather than causal relationships, given the absence of individual DEP exposure data and inherent methodological limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Through differential analysis and WGCNA, 24 differentially expressed genes and 194 chemical targets from ChEMBL were obtained, among which 14 overlapping genes were identified. GO and KEGG analyses indicated that DEP may contribute to PCD toxicity by regulating nucleotide synthesis and amino acid metabolism. Five core genes were screened via machine learning and SHAP analysis. Animal experiments verified that PLAU protein expression in DEP, TNBS, and DEP\u2009+\u2009TNBS groups was notably higher than in the control colon tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study systematically explores the potential associative links between DEP-related molecular dysregulation and PCD pathological alterations at the transcriptomic and tissue levels. The findings provide preliminary scientific references for understanding DEP-associated pediatric intestinal health risks and developing targeted preventive strategies for children's environmental health protection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1810586","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:36:10Z","timestamp":1787031370000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the impact of DEP on pediatric Crohn's disease using machine learning and molecular docking methods"],"prefix":"10.3389","volume":"14","author":[{"given":"Lei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Donghai County People\u2019s Hospital","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Donghai County People\u2019s Hospital","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Third Affiliated Hospital of Dali University","place":["Dali, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Donghai County People\u2019s Hospital","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.envint.2016.09.013","article-title":"A global assessment of phthalates burden and related links to health effects","volume":"97","author":"Katsikantami","year":"2016","journal-title":"Environ Int"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1007\/s00204-020-02748-9","article-title":"Risk assessment for humans using physiologically based pharmacokinetic model of diethyl phthalate and its major metabolite, monoethyl phthalate","volume":"94","author":"Jeong","year":"2020","journal-title":"Arch Toxicol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1111\/j.1539-6924.2006.00770.x","article-title":"What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?","volume":"26","author":"Wormuth","year":"2006","journal-title":"Risk Anal"},{"key":"B4","doi-asserted-by":"publisher","first-page":"105848","DOI":"10.1016\/j.envint.2020.105848","article-title":"Hazards of diethyl phthalate (DEP) exposure: a systematic review of animal toxicology studies","volume":"145","author":"Weaver","year":"2020","journal-title":"Environ Int"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1001\/jamapediatrics.2015.1982","article-title":"Inflammatory bowel disease in children and adolescents","volume":"169","author":"Rosen","year":"2015","journal-title":"JAMA Pediatr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1053\/j.gastro.2021.12.282","article-title":"Insightscope pediatric IBD epidemiology group; benchimol EI. 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