Altered Bile Acid Metabolism in Childhood Functional Constipation: Inactivation of Secretory Bile Acids by Sulfation in a Subset of Patients

被引:57
作者
Hofmann, Alan F. [1 ]
Loening-Baucke, Vera [2 ]
Lavine, Joel E. [3 ]
Hagey, Lee R. [1 ]
Steinbach, Joseph H. [1 ]
Packard, Christine A. [4 ]
Griffin, Terrance L. [4 ]
Chatfield, Dale A. [4 ]
机构
[1] Univ Iowa, Dept Med, Div Gastroenterol, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
[3] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
[4] San Diego State Univ, Dept Chem, San Diego, CA 92182 USA
关键词
Bile acid conjugation; Bile acid sulfation;
D O I
10.1097/MPG.0b013e31816920a6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objective: An elevated concentration in the colon of the primary bile acid chenodeoxycholic acid (CDCA) or the secondary bile acid deoxycholic acid (DCA) is known to induce water secretion, causing diarrhea. We hypothesized that of the many fecal bile acids. only CDCA and DCA function as endogenous laxatives: therefore. a decrease in their proportion may be a cause of childhood functional constipation. TO test this possibility, fecal bile acid composition was determined in children with functional constipation and in nonconstipated control children. Patients and Methods: Fecal samples were obtained front 207 children, 103 With functional constipation and 104 with a normal bowel habits. Bile acid classes were determined by use of electrospray ionization-single ion monitoring-mass spectrometry (ESI-SIM-MS), and individual bile acids were measured by gas chromatography (GC)MS (GC-MS). The structure of individual sulfated bile acids was obtained by use of fluid chromatography (LC)-MS (LC-MS). Results: By ESI-SIM-MS, the proportions of DCA did not differ in constipated children (n=73) front that ill control children (n=92), but monosulfated dihydroxy bile acids were greater (P < 0.05). The difference was attributable to 6 patients in the constipated group Whose major fecal bile acid by LC-MS was the 3-sulfate of CDCA. Sulfation of CDCA is known to abolish its secretory activity. By GC-MS, the bile acid profile was identical in the 2 groups. Conclusions: In most children with functional constipation, the fecal bile acid profile seems to be normal. There is a small Subset of children, however, whose dominant fecal bile acid is the 3-sulfate of CDCA. indicating, a novel disturbance in bile activity acid metabolism. Such sulfation abolishes the secretory activity of CDCA and may contribute to constipation. JPGN 47:598-606, 2008.
引用
收藏
页码:598 / 606
页数:9
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