Planar bile acids in health and disease

Bile acids are the amphipathic primary end-products of cholesterol metabolism that aid in digestion as well as participate in signal transduction in several hepatic and enteric pathways. Despite the reputation of bile acids as signaling molecules implicated in disease states such as cancer and diabetes, there remain numerous bile acid species that are weakly characterized in either physiological or pathological conditions. This review presents one such group: the flat or planar bile acids, a set of bile acids found in humans during infancy and occurring again during certain diseases. As their name implies, these molecules are structurally distinct from the typical human bile acids, retaining the planar structure of their cholesterol predecessor instead of bending or twisting at the A ring. This review defines these species of bile acids in detail and describes their presence in infancy, gestation, and in disease. The large gaps in research regarding the flat bile acids are highlighted and all available experimental knowledge collected as far as 60years ago is summarized. Further, the potential for these molecules as endogenous biomarkers of liver disease and injury is discussed. Finally, the flat bile salts found in humans are compared to the ancestral and evolutionary older bile salts, which similarly have a flat steroidal structure, as mechanisms of flat bile acid biosynthesis are explored.