Abstract:
BACKGROUND:Recent studies have suggested that the downregulation of pregnane X receptor (PXR) may contribute to the susceptibility and exacerbation of Crohn's disease (CD). Because bile acid malabsorption is one of the features of CD and bile acids are potential activators of PXR, we explored the relationship between bile acid malabsorption and PXR activities in patients with CD. METHODS:Twenty-one patients with CD (4 ileal-resected and 17 nonresected), 10 with ulcerative colitis (UC), and 26 healthy controls were studied. Serum biomarkers for the activity of CYP3A4, a target gene of PXR, and for cholesterol and bile acid metabolism were quantified by liquid chromatography-tandem mass spectrometry or enzyme-linked immunosorbent assay. RESULTS:The concentrations of 4β-hydroxycholesterol (4β-HC), a known marker for CYP3A4 activity, and those of 25-hydroxycholesterol (25-HC), another metabolite by CYP3A4, were significantly reduced in all patients with CD, especially in those with the history of ileal resection. The concentration of 7α-hydroxy-4-cholesten-3-one (C4), a marker for hepatic bile acid biosynthesis, was significantly elevated, whereas the levels of fibroblast growth factor 19 (FGF19), a marker for intestinal bile acid flux, were reduced in patients with CD compared with patients with UC and controls. A significant negative correlation was observed between 4β-HC or 25-HC and C4 concentrations in all patients with CD. CONCLUSIONS:The degree of bile acid malabsorption was closely associated with the deactivation of PXR in CD. Enterohepatic circulation of bile acids is a key factor for preservation of baseline activity of hepatointestinal PXR.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Iwamoto J,Saito Y,Honda A,Miyazaki T,Ikegami T,Matsuzaki Ydoi
10.1097/MIB.0b013e318281f423subject
Has Abstractpub_date
2013-05-01 00:00:00pages
1278-84issue
6eissn
1078-0998issn
1536-4844journal_volume
19pub_type
杂志文章abstract::The last 12 months have seen unprecedented progress in identifying the susceptibility genes that predispose to common disease in general and Crohn's disease in particular. Success has derived from the new technique of genome-wide association scanning in large panels of cases and controls. This has itself been made pos...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.20239
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abstract::Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive tract with heterogeneous clinical presentations. Crohn's is currently not a curable disease, and patients are faced with a lifetime of recurrent disease flare-ups and remissions. Management strategies for Crohn's must therefore be targete...
journal_title:Inflammatory bowel diseases
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
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更新日期:2016-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e3182a11958
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更新日期:2016-09-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20787
更新日期:2009-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa097
更新日期:2021-01-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,收录出版
doi:10.1002/ibd.21133
更新日期:2010-05-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20385
更新日期:2008-06-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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更新日期:2014-08-01 00:00:00
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pub_type: 杂志文章,实务指引,评审
doi:10.1002/ibd.20874
更新日期:2009-08-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0b013e318286f9f2
更新日期:2013-02-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21890
更新日期:2012-09-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200005000-00007
更新日期:2000-05-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2019-03-14 00:00:00
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pub_type: 杂志文章
doi:10.1097/00054725-200606000-00005
更新日期:2006-06-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izx109
更新日期:2018-05-18 00:00:00