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Duodenal bile acids as determinants of intestinal mucosal homeostasis and disease. Keely Simon,Talley Nicholas J Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society The duodenal epithelium plays a pivotal role in the uptake and transport of dietary nutrients while simultaneously acting as physical and biochemical barrier to protect against harmful bacteria and antigens. In the case of functional dyspepsia (FD), the duodenum is of particular interest, due to observed local immune involvement and the proximity to the stomach and exposure to acidopeptic secretions. Recent observations in FD pathophysiology, including those reported by Beeckmans et al in this issue of the journal, have identified a loss of barrier function in the duodenal epithelium, an altered duodenal microbiome and alterations in intestinal bile acid pools. Because FD symptoms coincide with food intake and, thus, secretion of bile acids, these findings may indicate loss or imbalance of bile-acid-microbiota-epithelial homeostasis as a process driving FD. Here, we review the evidence linking these observations to FD symptoms. 10.1111/nmo.13854