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Background

The aryl hydrocarbon receptor (AhR) is a cytosolic ligand dependent receptor that when activated down-regulates cellular inflammatory responses. Recognized dietary ligands of this receptor include omega-6 and omega-3 polyunsaturated fatty acids (omega-6 PUFA and omega-3 PUFA). Previous epidemiological studies have suggested that omega-6 PUFAs are potentially pro-inflammatory and omega-3 PUFAs anti-inflammatory in inflammatory bowel disease (IBD). However published data on the role of these fatty acids in disease prognosis and their mechanism of action is limited. The aim of this preliminary study was to assess whether AhR activity is associated with quiescent IBD status, and if serum levels of omega-6:omega-3 PUFAs in patients with clinically quiescent IBD can predict subsequent disease activity including flares.

Methods

Sixty patients with confirmed ulcerative colitis (UC) or Crohn’s Disease (CD) and quiescent disease activity (HBI < 4, SCCAI ≤ 3) were recruited into a prospective pilot study. Each patient was matched with age and gender specific non-IBD healthy controls. Serum at recruitment was measured for AhR activity utilizing the Promega dual-luciferase reporter assay. Values for cases and controls were then compared utilizing a linear regression model. Serum free fatty acid profile was determined by liquid gas chromatography following methylation and esterification. Disease activity over the subsequent 6 months was monitored at regular 2 monthly intervals, and if and when patients presented with a clinical flare. The association between serum omega-6, omega-3, omega-6:omega-3 ratios at recruitment and subsequent clinical activity was then determined using Student’s 2 sided t-test and a logistic regression model. All statistical analysis was performed using STATA IC-12.1 software.

Results

Thirty-six anti-TNF naïve patients with UC and 24 with CD were recruited along with 60 age, gender and smoking status matched healthy controls. Forty-one (68.3%) patients experienced a physician confirmed flare within 6 months. Mean HBI and SCCAI at recruitment were 0.67 (0–3). Mean duration of IBD was 11.52 years (SD 10.1, range 1–47 years). Mean level of luciferase expression was 0.1618 (SD 0.1132, range 0.1019–0.6292) in IBD cases at recruitment and 0.1206 (SD 0.0147, range 0.0696–0.1723) in healthy controls. There was no statistically significant difference (Coefficient, −0.0082, 95% CI −0.0422 to 0.0258, P > 0.05). Mean percentage at recruitment of total omega-6 PUFA in flared versus non flared patients was 33.23% to 29.71% (P = 0.003). Total omega-6:omega-3 ratios at onset in flared patients was 16.86% versus 12.55% in non-flares (P = 0.006). Omega-6 in IBD patients was associated with an increased risk of flare, OR 1.24 when adjusted for omega-3 PUFAs (95% CI 1.05–1.47, P = 0.01).

Conclusions

A higher omega-6:omega-3 ratio is predictive of disease activity within a 6 month period. In this preliminary study there was no statistically significant difference in serum AhR expression between quiescent IBD patients and healthy subjects, despite slightly higher levels detected in patients. This suggests that AhR receptor activity may be limited as a prognostic marker in quiescent IBD activity, however its role in active inflammation needs to be further explored. Further studies exploring the association between AhR activity and fatty acid levels are needed.

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Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.
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