Repository hosted by TU Delft Library

Home · Contact · About · Disclaimer ·
 

Determinants of postprandial plasma bile acid kinetics in human volunteers

Publication files not online:

Author: Fiamoncini, J. · Yiorkas, A.M. · Gedrich, K. · Rundle, M. · Alsters, S.I. · Roeselers, G. · Broek, T.J. van den · Clavel, T. · Lagkouvardos, I. · Wopereis, S. · Frost, G. · Ommen, B. van · Blakemore, A.I. · Daniel, H.
Type:article
Date:2017
Source:American Journal of Physiology - Gastrointestinal and Liver Physiology, 4, 313, G300-G312
Identifier: 781369
doi: doi:10.1152/ajpgi.00157.2017
Keywords: Biology · Bile acids · Mixed-meal tolerance test · Oral glucose tolerance test · Postprandial · SLCO1A2 · Chenodeoxycholic acid · Cholic acid · Deoxycholic acid · Genomic DNA · Glycine · Glycochenodeoxycholic acid · Glycocholic acid · Glycodeoxycholic acid · Glycoursodeoxycholic acid · Solute carrier organic anion transporter 1A2 · Taurine · Taurochenodeoxycholic acid · Taurocholic acid · Taurodeoxycholic acid · Taurolitocholic acid · Tauroursodeoxycholic acid · Unclassified drug · Ursodeoxycholic acid · Bile acid blood level · Bile acid synthesis · Clinical trial · Diet restriction · Dietary intake · Enterohepatic circulation · Feces microflora · Gene expression · Genome analysis · Kinetics · Liquid chromatography-mass spectrometry · Oral glucose tolerance test · Phenotype · Postprandial state · Quantitative analysis · Sex difference · Weight reduction · Whole exome sequencing · Blood · Controlled study · Physiology · Randomized controlled trial · Bile Acids and Salts · Fasting · Female · Humans · Male · Metabolic Clearance Rate · Middle Aged · Postprandial Period · Weight Loss · Biomedical Innovation · Healthy Living · Life · MSB - Microbiology and Systems Biology · ELSS - Earth, Life and Social Sciences

Abstract

Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual variability. Healthy men and women (n = 72, 62 ± 8 yr, mean ± SE) were enrolled into a 12-wk weight loss intervention. All subjects underwent an oral glucose tolerance test and a mixed-meal tolerance test before and after the intervention. BA were quantified in plasma by liquid chromatography-tandem mass spectrometry combined with whole genome exome sequencing and fecal microbiota profiling. Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma BA profiles. Fasting and postprandial BA profiles revealed high interindividual variability, and three main patterns in postprandial BA response were identified using multivariate analysis. Although the women enrolled were postmeno-pausal, effects of sex difference in BA response were evident. Exome data revealed the contribution of preselected genes to the observed interindividual variability. In particular, a variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases. Fecal microbiota analysis did not reveal evidence for a significant influence of bacterial diversity and/or composition on plasma BA profiles. The analysis of plasma BA profiles in response to two different dietary challenges revealed a high interindividual variability, which was mainly determined by genetics and sex difference of host with minimal effects of the microbiota. NEW & NOTEWORTHY Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma bile acid (BA) profiles. Despite high interindividual variability, three main patterns in postprandial BA response were identified using multivariate analysis. A variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases in response to both the oral glucose tolerance test and the mixed-meal tolerance test. © 2017, American Physiological Society. All rights reserved. Chemicals/CAS: chenodeoxycholic acid, 474-25-9; cholic acid, 32500-01-9, 361-09-1, 81-25-4; deoxycholic acid, 83-44-3; glycine, 56-40-6, 6000-43-7, 6000-44-8; glycochenodeoxycholic acid, 640-79-9; glycocholic acid, 475-31-0; glycodeoxycholic acid, 16409-34-0, 360-65-6; taurine, 107-35-7; taurochenodeoxycholic acid, 516-35-8; taurocholic acid, 145-42-6, 59005-70-8, 81-24-3; taurodeoxycholic acid, 1180-95-6, 516-50-7; tauroursodeoxycholic acid, 14605-22-2; ursodeoxycholic acid, 128-13-2, 2898-95-5; Bile Acids and Salts