{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:03:23Z","timestamp":1785866603737,"version":"3.56.0"},"reference-count":121,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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. Artif. Intell."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Intestinal fibrosis is a major complication of Crohn\u2019s disease (CD), a subtype of inflammatory bowel disease (IBD) driven by chronic inflammation and resulting in irreversible structural damage requiring surgery. However, the molecular differences between inflammatory and fibrotic CD remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we developed an integrated multi-omics framework combining transcriptomics, microbiome analysis, and generative AI to characterise transcriptomic differences across non-IBD (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f176), baseline CD (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f187), and fibrosis CD (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f85) tissues. Bulk and single-cell RNA-seq and 16S rRNA datasets were integrated, and machine learning identified disease-stage associated features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A shared set of 43 genes between baseline and fibrotic CD was organised into three modules: Module 1 (S100A8, TREM1, CXCL1) linked to innate immune activation which was upregulated in fibrosis CD; Module 2 (FABP6, MGAM, ALDOB) reflecting epithelial metabolic dysfunction which was upregulated in baseline CD; and Module 3 (CHI3L1, SAA2-SAA4, IL1RN) associated with epithelial stress and loss of barrier integrity. GSVA highlighted LCN2 and MMP3 across disease states. Microbiome analysis showed depletion of SCFA-producing genera (\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      ,\n                      <jats:italic>Anaerostipes<\/jats:italic>\n                      ,\n                      <jats:italic>Coprococcus<\/jats:italic>\n                      ,\n                      <jats:italic>Ruminococcus<\/jats:italic>\n                      ) and enrichment of\n                      <jats:italic>Bilophila<\/jats:italic>\n                      and\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      . Notably, LLM-guided augmentation improved model stability and facilitated the identification of key fibrosis-associated genes, including IL-23R, TNF-\u03b1, and TGF-\u03b2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that intestinal fibrosis in CD does not represent a separate molecular state, but a reconfigured inflammatory condition characterised by persistent immune activation, epithelial dysfunction, and altered host-microbiome interactions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frai.2026.1881820","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:01:21Z","timestamp":1785862881000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Generative AI-augmented transcriptomic and microbiome analysis across inflammatory and fibrotic disease states in Crohn\u2019s disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Daryll","family":"Philip","sequence":"first","affiliation":[{"name":"Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham Dubai","place":["Dubai, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Santos","sequence":"additional","affiliation":[{"name":"Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham Dubai","place":["Dubai, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudip","family":"Mondal","sequence":"additional","affiliation":[{"name":"Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]},{"name":"Centre for Health Data Research, University of Birmingham","place":["Birmingham, United Kingdom"]},{"name":"Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneen","family":"Alomar","sequence":"additional","affiliation":[{"name":"Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]},{"name":"Department of Research Laboratories, King Faisal Specialist Hospital & Research Centre","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Gkoutos","sequence":"additional","affiliation":[{"name":"Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]},{"name":"Centre for Health Data Research, University of Birmingham","place":["Birmingham, United Kingdom"]},{"name":"Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Animesh","family":"Acharjee","sequence":"additional","affiliation":[{"name":"Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham Dubai","place":["Dubai, United Arab Emirates"]},{"name":"Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]},{"name":"Centre for Health Data Research, University of Birmingham","place":["Birmingham, United Kingdom"]},{"name":"Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/S10620-011-1879-4","article-title":"Simvastatin attenuates intestinal fibrosis independent of the anti-inflammatory effect by promoting fibroblast\/myofibroblast apoptosis in the regeneration\/healing process from TNBS-induced colitis","volume":"57","author":"Abe","year":"2012","journal-title":"Dig. 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