Rebuttal to: Melancholé: the Dark Side of Bile Acids and Its Cellular Consequences

See Point-Counterpoint articles on pages 1474 and 1478. See Point-Counterpoint articles on pages 1474 and 1478. Bile acids are ancient molecules that have been known to modern science for more than a century. However, the depth of their role in pathophysiology only recently has been recognized. Studies in the past 2 decades, especially after identification of various bile acid receptors, first Farnesoid X Receptor, and later others, including G Protein-Coupled Bile Acid Receptor 1, have revolutionized our understanding of how deeply bile acids affect human health. These studies also have highlighted the fact that maintaining a healthy bile acid level is critical. As elegantly pointed out by Zhou and Anakk in their Point-Counter Point article,1Zhou W. Anakk S. Melancholé: the Dark Side of Bile Acids and Its Cellular Consequences.Cell Mol Gastroenterol Hepatol. 2022; 13: 1474-1476Google Scholar an increase in total bile acids can be toxic, and a change in bile acid composition can affect hepatic physiology. However, depletion of bile acids also can affect multiple processes, from digestion to regeneration to regulation of lipid metabolism. The fact that bile acids are active signaling molecules that are absolutely necessary for cross-organ communication (eg, as part of the gut–liver axis) makes them unique among the endobiotics and puts them in the same class as hormones and immune mediators. Thus, the basic principle of toxicology, espoused by the 14th century monk-physician Paracelsus, that "dose determines the poison," can be perfectly applied to the importance of bile acid maintenance.2Gallo M.A. Casarett & Doull's Toxicology: The Basic Science of Poisons. 8th Edition. McGraw Hill Education, 2013: 3-13Google Scholar Melancholé: The Dark Side of Bile Acids and Its Cellular ConsequencesCellular and Molecular Gastroenterology and HepatologyVol. 13Issue 5PreviewThe first bile acid, cholic acid, was discovered in 1848 from ox gallbladder, and the bile acid structure solved by Otto Wieland was recognized with the 1927 Nobel Prize in Chemistry.1 Primary bile acids are synthesized in the liver from cholesterol and conjugated to taurine or glycine for biliary secretion. Bile acid synthesis is catalyzed by approximately 17 enzymes via the classic or alternative pathways. The classic bile acid synthesis pathway is initiated by cholesterol 7α-hydroxylase (CYP7A1), followed by sterol 12α-hydroxylase (CYP8B1). Full-Text PDF Open Access