Page 60 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 3
Total BA concentrations were significantly higher in the portal vein compared to the peripheral circulation: 7.43 ± 7.2 vs 0.68 ± 0.5 mmol/ L, respectively (p 0.01). In peripheral veins BA concentrations were low and consisted of conjugated and unconjugated forms (Fig. 6). Portal BA concentrations were high and consisted mainly of conjugated forms, whereas the concentrations of unconjugated BAs were similar to those in the periphery (Fig. 6). Similar to pigs, LCA and conjugates were only detected in the portal vein. However, the human BA profile contained another secondary BA, i.e., deoxycholic acid (DCA), that circulated in the portal vein and the periphery and has been associated to insulin sensitivity [20-22].
Discussion
The aim of this study was to quantify porto-peripheral postprandial plasma BA profiles and transorgan flux. Fasting and postprandial peripheral and portal BA concentrations and fluxes are substantial which is supported by the enterohepatic cycle turnover of 12 times per day [23,45]. Physiological cycling of the BA pool may have advantages. In general, metabolic or endocrine cycles enable rapid physiological adaptations when demanded. In the case of the enterohepatic cycle, continuous cycling permits a swift increase of BAs (i.e., concentration) when needed postprandially. Continuous cycling of BAs may also prevent unlimited BA synthesis via FGF15/19 effects on CYP7A1, which is the rate-limiting enzyme of the major classical pathway in BA biosynthesis [24,25]. Liver and intestinal FXR KO murine models have shown that Cyp7a1 repression depends mainly on intestinal FXR activation via FGF15 [26,27]. Additionally, BAs inhibit Cyp7a1 via FXR and small heterodimer partner (SHP) in the liver [3,28,29].
The postprandial BA curves showed a large variability. La Russo et al. found that in humans peripheral conjugated CA forms show modest intra-individual variability with respect to the time of peak, however, peak height in these subjects showed up to ~30% variation [5]. Steiner et al. describe in detail the intra- and inter-individual variability in daily peripheral plasma BA concentrations of 4 healthy humans [30]. Intra-individual variability of postprandial BA curves and its determinants (e.g., gut luminal BA appearance, gut microbioma characteristics, BA transporter genotypes, BA synthetic capacity, gut motility and others) need to be investigated in future studies.
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