Insights Into Inflammatory Bowel Disease and Effects of Dietary Fatty Acid Intake With a Focus on Polyunsaturated Fatty Acids Using Preclinical Models

Author:

Smyth Matthew1,Lunken Genelle12,Jacobson Kevan123ORCID

Affiliation:

1. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Faculty of Medicine, British Columbia Children’s Hospital, University of British Columbia, B.C. , Vancouver, British Columbia , Canada , V6H 3V4

2. British Columbia Children Hospital Research Institute , Vancouver, British Columbia , Canada , V5Z 4H4

3. Department of Cellular and Physiological Sciences, University of British Columbia , Vancouver, British Columbia , Canada , V6T 2A1

Abstract

Abstract While the aetiology of inflammatory bowel disease (IBD) has been linked to genetic susceptibility coupled with environmental factors, the underlying molecular mechanisms remain unclear. Among the environmental factors, diet and the gut microbiota have been implicated as drivers of immune dysregulation in IBD. Indeed, epidemiologic studies have highlighted that the increase in incidence of IBD parallels the increase in dietary intake of omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and the change in balance of intake of n-6 to n-3 fatty acids. Experimental evidence suggests that the increase in n-6 PUFA intake increases cell membrane arachidonic acid, which is accompanied by the production of pro-inflammatory mediators as well as increased oxidative stress; together, this contributes to the development of chronic inflammation. However, it is also increasingly clear that some of the n-6 PUFA-derived mediators exert beneficial effects depending on the settings and timing of ingestion. In contrast to n-6, when n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid are incorporated into the cell membrane and are metabolized into less pro-inflammatory eicosanoids, as well as strong specialized pro-resolving mediators, which play a role in inflammation cessation. With a focus on preclinical models, we explore the relationship between dietary lipid, the gut microbiome, and intestinal inflammation.

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical)

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