Perfluoroalkyl Substances are increased in patients with Late-Onset Ulcerative colitis and induce Intestinal Barrier defects ex vivo in Murine Intestinal tissue

Abstract

Background and aim: Environmental factors are strongly implicated in late-onset inflammatory bowel disease. By measuring perfluoroalkyl substances we investigate whether high exposure correlates with late-onset inflammatory bowel disease, and disturbances of the bile acid pool. We further explore the effect of perfluoronoctanoic acid on intestinal barrier function in murine tissue. Methods: Serum levels of perfluoroalkyl substances and bile acids were assessed in matched samples from patients with ulcerative colitis (n=20) and Crohn's disease (n=20) diagnosed at the age of ≥55 years. Blood donors (n=20), were used as healthy controls. The metabolites were assessed by ultra-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer. Ex vivo exposure of perfluoronoctanoic acid in ileal and colonic murine tissue was assessed with the Ussing Chamber methodology (n=5). Results: The total amount of perfluoroalkyl substances was significantly increased in patients with ulcerative colitis compared to healthy controls or patients with Crohn's disease (p<0.05). Ex vivo exposure of 100 μM perfluoronoctanoic acid induced a significantly increased paracellular permeability across ileum (p<0.05) and an enhanced carbachol-induced ion secretion in colon. The distribution of bile acids as well as the correlation pattern between perfluoroalkyl substances and bile acids differed between patient groups and controls. Conclusion: Our results demonstrate that perfluoroalkyl substances levels are increased in patients with late-onset ulcerative colitis and might contribute to the disease by inducing a dysfunctional intestinal barrier or indirectly by interfering with the bile acid metabolism and thereby alter the intestinal barrier function.