{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:58:46Z","timestamp":1791406726032,"version":"4.3.3"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202906, 81972221, 81970716, 82170841, 82200921, 82370656, U21A20389, 82073640"],"award-info":[{"award-number":["82202906, 81972221, 81970716, 82170841, 82200921, 82370656, U21A20389, 82073640"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008750","name":"Shanghai Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC12018X04"],"award-info":[{"award-number":["SHDC12018X04"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2023-I2M-C&T-B-125"],"award-info":[{"award-number":["2023-I2M-C&T-B-125"]}]},{"name":"National Project for Promoting the Diagnosis and Treatment of Major Diseases"},{"DOI":"10.13039\/501100021791","name":"MDT","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021791","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The aim of this study was to investigate the gut microbial signatures and related pathophysiological implications in patients with Cushing's disease (CD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and methods<\/jats:title>\n                  <jats:p>Twenty-seven patients with CD and 45 healthy controls were enrolled. Based on obtained metagenomics data, we performed correlation, network study, and genome interaction group (GIG) analysis. Fecal metabolomics and serum enzyme linked immunosorbent assay (ELISA) analysis were conducted in dichotomized CD patients. Caco-2 cells were incubated with gradient concentrations of cortisol for subsequent transepithelial electrical resistance (TEER) measurement, FITC-dextran transwell permeability assay, qPCR, and western blot analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Gut microbial composition in patients with CD was notably different from that in healthy controls. Network analysis revealed that Eubacterium siraeum might serve as the core specie in the gut microbial system of CD patients. Subsequent GIG analysis identified the positive correlations between GIG9 and UFC. Further serum ELISA and fecal metabolomics uncovered that CD patients with elevated UFC levels were characterized with increased lipopolysaccharide binding protein (LBP). Moreover, remarkable positive association was found between LBP level and relative abundance of E. siraeum. TEER and FITC-dextran transwell assays demonstrated that hypercortisolism induced increased gut permeability. Further qPCR and western blot analysis suggested that dysregulated AhR\/Claudin 2 axis might be involved in the development of hypercortisolism-induced defective gut barrier function<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Disease activity associated dysbiosis and defective gut barrier might jointly facilitate the development of systemic inflammation in patients with CD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae139","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T06:31:46Z","timestamp":1729924306000},"page":"509-522","source":"Crossref","is-referenced-by-count":7,"title":["Concomitant gut dysbiosis and defective gut barrier serve as the bridges between hypercortisolism and chronic systemic inflammation in Cushing\u2019s disease"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5532-9389","authenticated-orcid":false,"given":"Ben","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai 200040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Melnikov","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University , Shanghai 200040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sichen","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Medical College, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University , Shanghai 200072 ,","place":["China"]},{"name":"Institute of Gut Microbiota Research and Engineering Development, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine , Shanghai 200072 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai 200040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai 200040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-5658","authenticated-orcid":false,"given":"Chenxing","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan 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