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 = 20) and Crohn’s disease (n = 20) diagnosed at the age of ≥55 years. Age and sex-matched blood donors (n = 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 = 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.
Correction Statement
This article has been corrected with minor changes. These changes do not impact the academic content of the article.
Acknowledgement
We thank Dr. Ciara Keogh and laboratory technician Jessica Sladek for skillful technical assistance in the Ussing laboratory, Davis, USA.
Disclosure statement
J. H. has served as an advisory board member or consultant for Abbvie, Aqilion, Celgene, Celltrion, Ferring, Gilead, Janssen, MSD, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma, and Vifor Pharma and received grant support from Janssen, MSD and Takeda. No potential conflict of interest was reported by the author(s).
Data availability statement
The data that support the findings of this study are available on request from the corresponding author, [IS], upon reasonable request.