Page 173 - Human Bile Acid Metabolism: a Postprandial Perspective

resistant to short-term disturbances. This leads to a slow timeframe in which interventions in bile acid metabolism lead to observable changes in the bile acid pool, and thus to a temporal disconnect between interventions and outcomes, making those outcomes difficult to interpret. We do know that alterations in bile acid synthesis can have large effects on the bile acid pool, as evidenced by the grossly abnormal bile acid pool compositions in patients with inborn errors of bile acid metabolism such as cerebrotendinous xanthomatosis. Unfortunately, these defects are exceedingly rare therefore not available for larger-scale studies. While in vitro and rodent models offer the opportunity to isolate molecular mechanisms, there is a need for more translational and physiological studies in human models of metabolic disease. The challenge will be to gain a direct view into the different compartments of the enterohepatic bile acid pool, as sampling the peripheral circulation alone does not capture the majority of bile acid-receptor interactions. Creative solutions involving clinicians, such as peroperative sampling of the portal vein or nuclear imaging techniques, will need to be found to sample the relevant compartments. Another avenue of great interest is the development of specific synthetic TGR5 and FXR agonists. Making these widely available for research would open up new opportunities to dissect human bile acid physiology.
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Discussion and future perspectives