Abstract
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder referred to gastroenterologists. Although the pathophysiology remains unclear, accumulating evidence points to the presence of low-level immune activation both in the gut and systemically. Circulating polyunsaturated fatty acids (PUFA) have recently attracted attention as being altered in a variety of disease states. Arachidonic acid (AA), in particular, has been implicated in the development of a pro-inflammatory profile in a number of immune-related disorders. AA is the precursor of a number of important immunomodulatory eicosanoids, including prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)). We investigated the hypothesis that elevated plasma AA concentrations in plasma contribute to the proposed pro-inflammatory profile in IBS. Plasma AA and related PUFA were quantified by gas chromatography analysis in IBS patients and controls. Both PGE(2) and LTB(4) were measured in serum using commercially available ELISA assays. AA concentrations were elevated in our patient cohort compared with healthy controls. Moreover, we demonstrated that this disturbance in plasma AA concentrations leads to downstream elevations in eicosanoids. Together, our data identifies a novel proinflammatory mechanism in irritable bowel syndrome and also suggests that elevated arachidonic acid levels in plasma may serve as putative biological markers in this condition.
Highlights
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder referred to gastroenterologists
The disorder is increasingly viewed as a disorder of the brain-gut axis, a construct describing a bidirectional interaction between the gastrointestinal tract (GIT), incorporating the intestinal epithelial barrier, the mucosa-associated lymphoid tissue (MALT), gut muscle and the enteric nervous system (ENS), and the central nervous system (CNS) [9, 10]
We have demonstrated that the consequences of the elevated Arachidonic acid (AA) levels include significant elevations in both prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in our IBS cohort
Summary
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder referred to gastroenterologists. The proposal that low-grade inflammation, as evidenced by the release of mast cell mediators and activation of lymphocytes in the colo-rectal mucosa and by the detection of elevated levels of pro-inflammatory cytokines in serum [8, 11,12,13], has provided a new dimension to this paradigm. The source of this low-grade inflammation, or immune activation, whether luminal or central, has remained elusive.
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