{"id":"https://openalex.org/W7172525103","doi":"https://doi.org/10.64898/2026.07.29.741535","title":"Epithelial-Intrinsic Alterations and Maladaptation to Luminal Metabolites Underlie Persistent Crohn\u2019s Disease Pathogenesis","display_name":"Epithelial-Intrinsic Alterations and Maladaptation to Luminal Metabolites Underlie Persistent Crohn\u2019s Disease Pathogenesis","publication_year":2026,"publication_date":"2026-08-04","ids":{"openalex":"https://openalex.org/W7172525103","doi":"https://doi.org/10.64898/2026.07.29.741535"},"language":"en","primary_location":{"id":"doi:10.64898/2026.07.29.741535","doi":"https://doi.org/10.64898/2026.07.29.741535","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.07.29.741535","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.64898/2026.07.29.741535","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5144396734","display_name":"Jianqiao Liu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jianqiao Liu","raw_affiliation_strings":["Department of Chemistry, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101448008","display_name":"Ran Zhou","orcid":"https://orcid.org/0000-0001-7756-2755","observed_orcids":["https://orcid.org/0000-0001-7756-2755"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ran Zhou","raw_affiliation_strings":["Department of Medicine, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056818748","display_name":"Jason Koval","orcid":"https://orcid.org/0000-0003-4270-0534","observed_orcids":["https://orcid.org/0000-0003-4270-0534"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jason Koval","raw_affiliation_strings":["Department of Medicine, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061140470","display_name":"Peter S. Carbonetto","orcid":"https://orcid.org/0000-0003-1144-6780","observed_orcids":["https://orcid.org/0000-0003-1144-6780"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Peter Carbonetto","raw_affiliation_strings":["Department of Human Genetics, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Human Genetics, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020906569","display_name":"Candace M. Cham","orcid":"https://orcid.org/0000-0001-7135-949X","observed_orcids":["https://orcid.org/0000-0001-7135-949X"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Candace M. Cham","raw_affiliation_strings":["Department of Medicine, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057768752","display_name":"Ashley M. Sidebottom","orcid":"https://orcid.org/0000-0002-8670-9090","observed_orcids":["https://orcid.org/0000-0002-8670-9090"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ashley M. Sidebottom","raw_affiliation_strings":["Duchossois Family Institute, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Duchossois Family Institute, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036504609","display_name":"Matthew Stephens","orcid":"https://orcid.org/0000-0001-5397-9257","observed_orcids":["https://orcid.org/0000-0001-5397-9257"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Matthew Stephens","raw_affiliation_strings":["Department of Human Genetics, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Human Genetics, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008444160","display_name":"Sebastian Pott","orcid":"https://orcid.org/0000-0002-4118-6150","observed_orcids":["https://orcid.org/0000-0002-4118-6150"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sebastian Pott","raw_affiliation_strings":["Department of Medicine, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042231260","display_name":"Eugene B. Chang","orcid":"https://orcid.org/0000-0001-5972-8248","observed_orcids":["https://orcid.org/0000-0001-5972-8248"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eugene B. Chang","raw_affiliation_strings":["Department of Medicine, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5001473989","display_name":"Anindita Basu","orcid":"https://orcid.org/0000-0001-9468-3727","observed_orcids":["https://orcid.org/0000-0001-9468-3727"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Anindita Basu","raw_affiliation_strings":["Department of Medicine, University of Chicago, Chicago IL, 60637, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Chicago, Chicago IL, 60637, USA","institution_ids":["https://openalex.org/I40347166"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5001473989"],"corresponding_institution_ids":["https://openalex.org/I40347166"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10134","display_name":"Inflammatory Bowel Disease","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2715","display_name":"Gastroenterology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10134","display_name":"Inflammatory Bowel Disease","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2715","display_name":"Gastroenterology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10066","display_name":"Gut microbiota and health","score":0.0012000000569969416,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11289","display_name":"Single-cell and spatial transcriptomics","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/crohn-s-disease","display_name":"Crohn's disease","score":0.9890000224113464},{"id":"https://openalex.org/keywords/intestinal-epithelium","display_name":"intestinal epithelium","score":0.9470000267028809},{"id":"https://openalex.org/keywords/intestinal-organoids","display_name":"intestinal organoids","score":0.675000011920929},{"id":"https://openalex.org/keywords/chromatin-remodeling","display_name":"chromatin remodeling","score":0.703000009059906},{"id":"https://openalex.org/keywords/remission","display_name":"remission","score":0.7390000224113464},{"id":"https://openalex.org/keywords/single-cell-rna-sequencing","display_name":"single-cell RNA sequencing","score":0.7099999785423279},{"id":"https://openalex.org/keywords/single-cell-atac-seq","display_name":"single-cell ATAC-seq","score":0.9959999918937683}],"concepts":[{"id":"https://openalex.org/C31695470","wikidata":"https://www.wikidata.org/wiki/Q11293125","display_name":"Organoid","level":2,"score":0.7713000178337097},{"id":"https://openalex.org/C2780942790","wikidata":"https://www.wikidata.org/wiki/Q372016","display_name":"Pathogenesis","level":2,"score":0.6503000259399414},{"id":"https://openalex.org/C182025440","wikidata":"https://www.wikidata.org/wiki/Q4864574","display_name":"Maladaptation","level":2,"score":0.6007000207901001},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5756000280380249},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.5418000221252441},{"id":"https://openalex.org/C529295009","wikidata":"https://www.wikidata.org/wiki/Q41301","display_name":"Epithelium","level":2,"score":0.47290000319480896},{"id":"https://openalex.org/C24998067","wikidata":"https://www.wikidata.org/wiki/Q4114622","display_name":"Stimulation","level":2,"score":0.4205999970436096},{"id":"https://openalex.org/C2781077229","wikidata":"https://www.wikidata.org/wiki/Q509615","display_name":"Intestinal epithelium","level":3,"score":0.4077000021934509},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3714999854564667},{"id":"https://openalex.org/C3019368612","wikidata":"https://www.wikidata.org/wiki/Q17154506","display_name":"Intestinal mucosa","level":2,"score":0.3671000003814697},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3626999855041504},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.3433000147342682},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.34119999408721924},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.3361000120639801},{"id":"https://openalex.org/C83640560","wikidata":"https://www.wikidata.org/wiki/Q180951","display_name":"Chromatin","level":3,"score":0.33079999685287476},{"id":"https://openalex.org/C2992264114","wikidata":"https://www.wikidata.org/wiki/Q1394551","display_name":"Clinical disease","level":3,"score":0.31470000743865967},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.30059999227523804}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.07.29.741535","doi":"https://doi.org/10.64898/2026.07.29.741535","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.07.29.741535","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.07.29.741535","doi":"https://doi.org/10.64898/2026.07.29.741535","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.07.29.741535","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.98580002784729}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":72,"referenced_works":["https://openalex.org/W1902027874","https://openalex.org/W1965157206","https://openalex.org/W1965725744","https://openalex.org/W1998470464","https://openalex.org/W2002513358","https://openalex.org/W2085284704","https://openalex.org/W2111065008","https://openalex.org/W2122031852","https://openalex.org/W2122292170","https://openalex.org/W2123879591","https://openalex.org/W2130410032","https://openalex.org/W2146955237","https://openalex.org/W2161377277","https://openalex.org/W2171808845","https://openalex.org/W2179438025","https://openalex.org/W2341031032","https://openalex.org/W2342314812","https://openalex.org/W2570178861","https://openalex.org/W2571503386","https://openalex.org/W2620676965","https://openalex.org/W2750049634","https://openalex.org/W2766609999","https://openalex.org/W2767423581","https://openalex.org/W2802205848","https://openalex.org/W2804176448","https://openalex.org/W2808722470","https://openalex.org/W2817838603","https://openalex.org/W2886629595","https://openalex.org/W2888169023","https://openalex.org/W2916244827","https://openalex.org/W2948469692","https://openalex.org/W2949177718","https://openalex.org/W2950975031","https://openalex.org/W2951232102","https://openalex.org/W2952603284","https://openalex.org/W2958554910","https://openalex.org/W2963622568","https://openalex.org/W2973682581","https://openalex.org/W2988716798","https://openalex.org/W3006764495","https://openalex.org/W3042128398","https://openalex.org/W3045120722","https://openalex.org/W3108788068","https://openalex.org/W3109700903","https://openalex.org/W3120576609","https://openalex.org/W3123185162","https://openalex.org/W3141309774","https://openalex.org/W3149417142","https://openalex.org/W3184907113","https://openalex.org/W4211050664","https://openalex.org/W4211138554","https://openalex.org/W4244626580","https://openalex.org/W4293475192","https://openalex.org/W4296039770","https://openalex.org/W4297981002","https://openalex.org/W4306411778","https://openalex.org/W4318167744","https://openalex.org/W4318755347","https://openalex.org/W4363673883","https://openalex.org/W4390947551","https://openalex.org/W4392364674","https://openalex.org/W4396773120","https://openalex.org/W4399552536","https://openalex.org/W4401794418","https://openalex.org/W4403619489","https://openalex.org/W4405995908","https://openalex.org/W4409027075","https://openalex.org/W4411090890","https://openalex.org/W6901820054","https://openalex.org/W7141375108","https://openalex.org/W7164830509","https://openalex.org/W7214358496"],"related_works":["https://openalex.org/W2320034725","https://openalex.org/W2325445192","https://openalex.org/W4415388974","https://openalex.org/W2914095307","https://openalex.org/W4399552536","https://openalex.org/W2950224889","https://openalex.org/W4404408687","https://openalex.org/W2792641862","https://openalex.org/W4403889355","https://openalex.org/W3178220768"],"abstract_inverted_index":{"Summary":[0],"In":[1,156],"patients":[2,56,141,166],"with":[3,57,97],"Crohn\u2019s":[4,61,164],"disease,":[5,62],"the":[6,35,109,115],"noninflamed":[7,51],"intestinal":[8,52,74,86],"epithelium":[9],"exhibits":[10],"inflammation-like":[11],"transcriptional":[12,172],"signatures":[13,145],"that":[14,118,130,189],"persist":[15,119],"even":[16,137],"during":[17],"clinical":[18],"remission.":[19],"However,":[20],"it":[21],"is":[22,27],"unclear":[23],"whether":[24],"this":[25],"signature":[26],"due":[28],"to":[29,34,68,106,158,181],"sustained":[30],"environmental":[31,42],"triggers":[32],"or":[33],"epithelium\u2019s":[36],"intrinsic":[37,116],"immunological":[38],"adaptions.":[39],"To":[40],"disentangle":[41],"and":[43,59,81,88,94,114,153,174,199],"cell-intrinsic":[44,197],"effects":[45,110],"on":[46],"disease":[47,135,165],"signatures,":[48],"we":[49],"used":[50],"tissue":[53,147],"biopsies":[54],"from":[55,85,89,124,140,146,163],"active":[58],"inactive":[60],"as":[63,65],"well":[64],"control":[66,160],"donors,":[67],"generate":[69],"donor-matched":[70],"organoids":[71,92,162],"enriched":[72],"for":[73],"epithelial":[75,191],"cells.":[76],"We":[77,128],"collected":[78],"single-cell":[79,82],"RNA-seq":[80],"ATAC-seq":[83],"data":[84],"tissues,":[87],"their":[90,125],"matched":[91],"before":[93],"after":[95,179],"stimulation":[96],"luminal":[98,183],"metabolites":[99],"of":[100,111,151,170],"patients.":[101],"This":[102],"approach":[103],"allowed":[104],"us":[105],"distinguish":[107],"between":[108],"extrinsic":[112],"factors":[113],"alterations":[117],"when":[120,138],"cells":[121,132,148],"are":[122,193],"removed":[123],"local":[126],"environment.":[127],"found":[129],"organoid":[131],"retained":[133],"epithelial-autonomous":[134],"phenotypes,":[136],"derived":[139],"in":[142],"remission,":[143],"whereas":[144],"showed":[149],"evidence":[150],"immune-":[152],"microbial-epithelial":[154],"crosstalk.":[155],"contrast":[157],"healthy":[159],"organoids,":[161],"exhibited":[167],"selective":[168],"activation":[169],"disease-associated":[171,190],"changes":[173],"environment-responsive":[175],"inflammatory":[176],"chromatin":[177],"remodeling":[178],"exposure":[180],"patient-derived":[182],"metabolites.":[184],"Overall,":[185],"our":[186],"study":[187],"suggests":[188],"states":[192],"shaped":[194],"by":[195],"both":[196],"dysregulation":[198],"microenvironmental":[200],"cues.":[201]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-08-06T00:00:00"}