{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:27:15Z","timestamp":1789615635024,"version":"build-2803163510"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["21153MFDS602"],"award-info":[{"award-number":["21153MFDS602"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Program of the National Research Foundation"},{"name":"Korean government","award":["NRF-2023R1A2C1003557"],"award-info":[{"award-number":["NRF-2023R1A2C1003557"]}]},{"DOI":"10.13039\/501100013173","name":"GRRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013173","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gyeonggi","award":["GRRCAjou2023-B01"],"award-info":[{"award-number":["GRRCAjou2023-B01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammatory bowel disease remains an enigma in terms of its etiology, with breakdown of the intestinal barrier attributed to the elusive leaky gut syndrome. In this study, we investigated the role of interplay between hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AhR) in maintaining intestinal barrier homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An enteroid system and AhR-deficient mouse models were used, with HIF stabilized by a prolyl hydroxylase inhibitor. Barrier function of enteroids was assessed by measuring size, budding number, Ki-67+ cell proliferation, and tight junction\u2013related gene expression. In mice, gut barrier function was evaluated by histology, bacterial translocation, and barrier-related transcripts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AhR-deficient enteroids derived from the small intestinal crypts of AhR-deficient mice showed increased cellular proliferation and budding and decreased expression of tight junction molecules that regulate barrier permeability. Moreover, AhR-deficient mice showed enhanced bacterial translocation from normal flora in the mesenteric lymph nodes and spleen and elevated serum endotoxin concentrations, indicating enhanced barrier permeability in vivo. Stabilizing HIFs through a prolyl hydroxylase inhibitor restored the expression of barrier molecules in AhR-deficient enteroids and decreased the translocation of enteric bacteria, suggesting the restoration of gut barrier function<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggested that high intestinal permeability due to AhR deficiency can be ameliorated by the stabilization of HIFs, indicating a compensatory role in barrier maintenance. This discovery holds promise for advancing therapeutic strategies for patients with gut permeability issues such as inflammatory bowel disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izaf155","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:58:25Z","timestamp":1751443105000},"page":"2875-2885","source":"Crossref","is-referenced-by-count":2,"title":["Hypoxia-Inducible Factor Signaling Compensates for Aryl Hydrocarbon Receptor in Maintaining Gut Barrier Integrity"],"prefix":"10.1093","volume":"31","author":[{"given":"Min-Gyu","family":"Gwak","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mee-Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biohealth Regulatory Science, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Hee","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-In","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]},{"name":"Research Institute of Pharmaceutical Science and Technology, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]},{"name":"Department of Biohealth Regulatory Science, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]},{"name":"Research Institute of Pharmaceutical Science and Technology, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7336-9245","authenticated-orcid":false,"given":"Sun-Young","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 16499,","place":["South Korea"]},{"name":"Department of Biohealth Regulatory Science, College of Pharmacy, Ajou University , Suwon, Gyeonggi-do 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