Print Email Facebook Twitter Determinants of postprandial plasma bile acid kinetics in human volunteers Title Determinants of postprandial plasma bile acid kinetics in human volunteers Author Fiamoncini, J. Yiorkas, A.M. Gedrich, K. Rundle, M. Alsters, S.I. Roeselers, G. van den Broek, T.J. Clavel, T. Lagkouvardos, I. Wopereis, S. Frost, G. van Ommen, B. Blakemore, A.I. Daniel, H. Publication year 2017 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 Subject LifeMSB - Microbiology and Systems BiologyELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingBile acidsMixed-meal tolerance testOral glucose tolerance testPostprandialSLCO1A2Chenodeoxycholic acidCholic acidDeoxycholic acidGenomic DNAGlycineGlycochenodeoxycholic acidGlycocholic acidGlycodeoxycholic acidGlycoursodeoxycholic acidSolute carrier organic anion transporter 1A2TaurineTaurochenodeoxycholic acidTaurocholic acidTaurodeoxycholic acidTaurolitocholic acidTauroursodeoxycholic acidUnclassified drugUrsodeoxycholic acidBile acid blood levelBile acid synthesisClinical trialDiet restrictionDietary intakeEnterohepatic circulationFeces microfloraGene expressionGenome analysisKineticsLiquid chromatography-mass spectrometryOral glucose tolerance testPhenotypePostprandial stateQuantitative analysisSex differenceWeight reductionWhole exome sequencingBloodControlled studyPhysiologyRandomized controlled trialBile Acids and SaltsFastingFemaleHumansMaleMetabolic Clearance RateMiddle AgedPostprandial PeriodWeight Loss To reference this document use: http://resolver.tudelft.nl/uuid:8de9f6cd-2395-4ce7-ba8f-45ea830f67c4 DOI https://doi.org/10.1152/ajpgi.00157.2017 TNO identifier 781369 ISSN 0193-1857 Source American Journal of Physiology - Gastrointestinal and Liver Physiology, 313 (4), G300-G312 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.