Model-based data analysis of individual human postprandial plasma bile acid responses indicates a major role for the gallbladder and intestine

Emma C.E. Meessen, Fianne L P Sips, Hannah M. Eggink, Martijn Koehorst, Johannes A. Romijn, Albert K. Groen, Natal A.W. van Riel, Maarten R. Soeters (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

BACKGROUND: Bile acids are multifaceted metabolic compounds that signal to cholesterol, glucose, and lipid homeostasis via receptors like the Farnesoid X Receptor (FXR) and transmembrane Takeda G protein-coupled receptor 5 (TGR5). The postprandial increase in plasma bile acid concentrations is therefore a potential metabolic signal. However, this postprandial response has a high interindividual variability. Such variability may affect bile acid receptor activation.

METHODS: In this study, we analyzed the inter- and intraindividual variability of fasting and postprandial bile acid concentrations during three identical meals on separate days in eight healthy lean male subjects using a statistical and mathematical approach.

MAIN FINDINGS: The postprandial bile acid responses exhibited large interindividual and intraindividual variability. The individual mathematical models, which represent the enterohepatic circulation of bile acids in each subject, suggest that interindividual variability results from quantitative and qualitative differences of distal active uptake, colon transit, and microbial bile acid transformation. Conversely, intraindividual variations in gallbladder kinetics can explain intraindividual differences in the postprandial responses.

CONCLUSIONS: We conclude that there is considerable inter- and intraindividual variation in postprandial plasma bile acid levels. The presented personalized approach is a promising tool to identify unique characteristics of underlying physiological processes and can be applied to investigate bile acid metabolism in pathophysiological conditions.

Original languageEnglish
Article numbere14358
Number of pages14
JournalPhysiological Reports
Volume8
Issue number5
DOIs
Publication statusPublished - 1 Mar 2020

Keywords

  • digital twinning
  • postprandial bile acid metabolism
  • interindividual variability
  • mathematical modeling
  • intraindividual variability
  • mixed meal test

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