Gallstone Disease and Cancer Risk: Finding the Bug in the System Kjetil Søreide  Gastroenterology  Volume 152, Issue 8, Pages 1825-1828 (June 2017) DOI: 10.1053/j.gastro.2017.04.028 Copyright © 2017 AGA Institute Terms and Conditions

Figure 1 Putative mechanisms in the gut–microbiota–liver axis leading to gallbladder disease and carcinogenesis in several organ sites. (A) Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor in the ileum and liver. Bile acids are important signaling molecules in the host, as they interact either locally or systemically with specific cellular receptors, in particular farnesoid X receptor and TGR5. These signaling functions influence systemic lipid and cholesterol metabolism, energy metabolism, immune homeostasis, and intestinal electrolyte balance. (B) Common risk factors for gallstone formation and cancer. Altered microbiome may be an effect and a cause of bile acid composition and gallstone development. Changes may further effect the intestinal epithelium, with progressive cellular and molecular alterations in carcinogenesis. Cancer in certain organ sites, such as breast, could be explained by altered metabolic or endocrine pathways. The most apparent mechanism between gallstone disease and cancer may be linked with altered microbiota, changes in bile metabolism, and subsequent cellular and molecular effects in the proximal colon, because this subsite is associated with particular molecular pathways described in the consensus molecular subtype studies. Gastroenterology 2017 152, 1825-1828DOI: (10.1053/j.gastro.2017.04.028) Copyright © 2017 AGA Institute Terms and Conditions