Altered colonic mucosal availability of n-3 and n-6 polyunsaturated fatty acids in ulcerative colitis and the relationship to disease activity

Abstract

Background and aims: The polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA.

Methods: Colonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, respectively.

Results: Biopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p<0.001) and lower EPA (p<0.010) contents and a higher AA:EPA ratio (p<0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and α-linolenic acid (α-LNA) contents (all p<0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, α-LNA and EPA (negative correlations).

Conclusions: Higher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used.

Keywords: 5-ASA; 5-aminosalicylic acid; AA; Arachidonic acid; Cytokine; DHA; DPA; EI-SIM; EPA; Eicosanoid; Eicosapentaenoic acid; FA; GC/MS; HPLC; Inflammation; LA; LC/MS; LT; PG; PPARγ; PUFA; SPE; UC; alpha linolenic acid; arachidonic acid; docosahexaenoic acid; docosapentaenoic acid; eicosapentaenoic acid; electron impact selective ion monitoring; fatty acid; gas chromatography mass spectrometry; high performance liquid chromatography; leukotrienes; linoleic acid; liquid chromatography mass spectrometry; peroxisome proliferator activator receptor γ; polyunsaturated fatty acid; prostaglandins; solid phase extraction; ulcerative colitis; α-LNA.