Perfluoroalkyl substances are increased in patients with late-onset ulcerative colitis and induce intestinal barrier defects ex vivo in murine intestinal tissue

Frida Fart, Samira Salihović, Aidan McGlinchey, Melanie G. Gareau, Matej Orešič, Jonas Halfvarson, Tuulia Hyötyläinen, Ida Schoultz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1286-1295
Number of pages10
JournalScandinavian Journal of Gastroenterology
Volume56
Issue number11
DOIs
StatePublished - 2021

Keywords

  • bile acids
  • inflammatory bowel disease
  • intestinal barrier function
  • PFAS
  • ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

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