Page 170 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 9
Secondly, timing matters. It has previously been published that postprandial bile acid concentrations in peripheral plasma are crucially dependent on intestinal transit time (Meessen et al., 2020), which may differ both between and within test subjects, dependent on genetics and behavior leading up to study days, leading to signal interference. This is again illustrated by the work of LaRusso and Steiner, where the arrival of bile acids in the sampled compartment, peripheral plasma, appeared to vary widely between and within subjects.
A third factor is the striking interindividual difference in bile acid pool composition and conjugation state in both healthy and diseased subjects. This may be explained by heterogeneity of the enterohepatic enzymatic apparatus tasked with bile acid circulation, arising from not only genetic variation but also anatomic, dietary and behavioral factors as well as the host microbiome. We speculate that the existence of these different bile acid “phenotypes” could be a contributing factor in the development of metabolic disease at a later age. To explore this further, more research is needed into the determinants of bile acid pool composition, i.e. enteral and hepatic transport kinetics, intestinal transit time, and bile acid synthesis.
Ultimately, the wide array of individual bile acid pool compositions found in otherwise healthy subjects may be indicative of the absence of a strong causal link between bile acid pool composition and the pathophysiology of energy metabolism.
Bile acid responses to metabolic challenges
A point of interest of current bile acid research is the suggested involvement of bile acids in the pathophysiology of obesity and DM2. As such, bile acid biology has been shown to be altered in patients with obesity and/or DM2 (Brufau et al., 2010; Glicksman et al., 2010; Haeusler et al., 2013; Sonne et al., 2016; Vincent et al., 2013). We set out to characterize the postprandial bile acid response in a selection of models of metabolic derangement.
We showed that in healthy, lean, male subjects, bile acid levels peak postprandially in unison with insulin and GLP-1. After a 40-h fast, an intervention known to powerfully induce insulin resistance in a short time-span, bile acid responses were unaffected. This suggests that the acutely developed increase in postprandial glucose and insulin levels in these fasting subjects, denoting insulin resistance,
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