Perfluoroalkyl substances are increased in patients with late-onset ulcerative colitis and induce intestinal barrier defectsex vivoin murine intestinal tissue

Abstract

Background: Environmental factors are strongly implicated in late-onset of inflammatory bowel disease. Here, we investigate whether high levels of perfluoroalkyl substances are associated with (1) late-onset inflammatory bowel disease, and (2) disturbances of the bile acid pool. We further explore the effect of the specific perfluoroalkyl substance perfluorooctanoic acid on intestinal barrier function in murine tissue. Methods: Serum levels of perfluoroalkyl substances and bile acids were assessed by ultra-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer in matched samples from patients with ulcerative colitis (n ¼ 20) and Crohn's disease (n ¼ 20) diagnosed at the age of !55 years. Age and sex-matched blood donors (n ¼ 20), were used as healthy controls. Ex vivo Ussing chamber experiments were performed to assess the effect of perfluorooctanoic acid on ileal and colonic murine tissue (n ¼ 9). Results: The total amount of perfluoroalkyl substances was significantly increased in patients with ulcerative colitis compared to healthy controls and patients with Crohn's disease (p < .05). Ex vivo exposure to perfluorooctanoic acid induced a significantly altered ileal and colonic barrier function. The distribution of bile acids, as well as the correlation pattern between (1) perfluoroalkyl substances and (2) bile acids, differed between patient and control groups. Discussion: Our results demonstrate that perfluoroalkyl substances levels are increased in patients with late-onset ulcerative colitis and may contribute to the disease by inducing a dysfunctional intestinal barrier.

PFOA/PFOS Facilitated Intestinal Fatty Acid Absorption by Activating the PPARα Pathway: Insights from Organoids Model

“…22 Previous studies indicated that PFOS could induce intestinal barrier defects, resulting in an enhanced permeability of intestinal epithelium. 38 Moreover, Liang et al revealed a significant decrease of villus height and crypt depth in the proximal duodenum and jejunum of rats after PFOS exposure. 14 However, in our experiments, PFOA/PFOS did not affect the formation of organoids and budding structures except when exposed to very high concentrations.…”

“…Previous studies have shown that PFOA/PFOS could induce intestinal barrier defects and thus interfere with the permeability of the intestinal epithelium. 38 To further prove whether the effects of PFOA/PFOS on fatty acid absorption were related to intestinal permeability, a permeability assay for intestinal organoids was performed. As shown in Figure 3B, PFOA and PFOS treatment at concentrations of 100 μmol/L and 200 μmol/L did not significantly affect the average fluorescence intensity of PI in intestinal organoids, indicating that PFOA and PFOS exposure did not affect the permeability of intestinal organoids.…”

In vitro models and ex vivo systems used in inflammatory bowel disease

“…Presence of electrodes to measure transport of ion [ 147 ]. Used to study intestinal permeability [ 149 ]. Used to study host-microbiome interactions [ 151 ].…”

“…Used to study host-microbiome interactions [ 151 ]. Use of both animal and human tissue possible [ 149 ]. Physiology of receptors can easily be studied [ 157 – 160 ].…”

“…Clinical studies on rectal biopsies of patients with cystic fibrosis have demonstrated that ion transport function may be effectively assessed using the Ussing chamber [ 148 ]. Gut integrity and intestinal permeability investigations on mouse and human colon biopsies have also been published [ 149 ]. The use of the Ussing chamber also assisted the researchers in determining that in the instance of a human colon, the left colon had more permeability than the right colon [ 145 ].…”