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Perfluoroalkyl substances are increased in patients with late-onset ulcerative colitis and induce intestinal barrier defects ex vivo in murine intestinal tissue
Örebro University, School of Medical Sciences.ORCID iD: 0000-0002-5990-0009
Örebro University, School of Medical Sciences. Örebro University, School of Science and Technology.ORCID iD: 0000-0001-5752-4196
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-6682-6030
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
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2021 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 56, no 11, p. 1286-1295Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Taylor & Francis, 2021. Vol. 56, no 11, p. 1286-1295
Keywords [en]
PFAS, bile acids, inflammatory bowel disease, intestinal barrier function, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-93618DOI: 10.1080/00365521.2021.1961306ISI: 000684451500001PubMedID: 34383611Scopus ID: 2-s2.0-85112297285OAI: oai:DiVA.org:oru-93618DiVA, id: diva2:1585086
Funder
Swedish Research Council, 2016-05176European CommissionSwedish Research Council Formas, 2019-00869
Note

Funding Agencies:

Faculty of Medicine and Health, Örebro University ORU2018/04457

Bo Rydin foundation F0514

Örebro Hospital Research Foundation OLL-790011

Available from: 2021-08-16 Created: 2021-08-16 Last updated: 2025-02-11Bibliographically approved
In thesis
1. The Ageing Gut, in Health and Disease
Open this publication in new window or tab >>The Ageing Gut, in Health and Disease
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is a global ageing phenomenon, which stress the importance for an improved health for the increased population of older adults. One important factor for a good health is a well-functioning gut. Hence, this thesisinvestigates several aspects of gut health for older adults, spanning from overall gut health in community-dwelling older adults, to investigating a gut disease model: inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis. 

When investigating community-dwelling older adults, gastrointestinal symptoms were found to be common and correlated to a lower experience of well-being. In addition, more than half of the population did not reach the recommended intake of several macronutrients, including protein and fibre. Compared to a group of active older adults, still practising orienteering, i.e., senior orienteers, community-dwelling older adult’s further showed signs of a less healthier gut microbiota, including lower levels of Faecalibacterium prausnitzii.

By investigating the disease model of inflammatory bowel disease, later onset of Crohn’s disease seemed to have less hyperresponsive adaptive immune response toward the own gut microbiota, which seems to be due to a less genetic predisposition among later onset individuals. Interestingly, an environmental pollutant, per- and polyfluoroalkyl substances (PFAS), was increased in the serum of late-onset ulcerative colitis patients compared to healthy controls. A higher level of PFAS further correlated to a disturbed bile acid pool. In addition, PFAS induced an increased intestinal permeability across ileal and colonic murine tissue. 

In conclusion, the work included in this thesis further emphasises the importance of a maintained gut health. In addition, the work highlights diet, an active life-style, gut microbiota and environmental factors, for example PFAS, as targets of future interventions studies with the aim to improve gut health and overall health among older adults. 

Place, publisher, year, edition, pages
Örebro: Örebro University, 2022. p. 90
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 268
Keywords
Older adults, gut health, gastrointestinal symptoms, gut microbiota, nutrition, physical activity, inflammatory bowel disease, late-onset, per- and polyfluoroalkyl substances
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-98220 (URN)9789175294513 (ISBN)
Public defence
2022-06-16, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (Swedish)
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Supervisors
Available from: 2022-03-23 Created: 2022-03-23 Last updated: 2022-06-16Bibliographically approved

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Fart, FridaSalihovic, SamiraMcGlinchey, Aidan JOresic, MatejHalfvarson, JonasHyötyläinen, TuuliaSchoultz, Ida

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