Marked elevations in pro-inflammatory polyunsaturated fatty acid metabolites in females with irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a common and potentially disabling, though nonfatal, medical disorder that can affect up to 20% of the population. It is the most common functional gastrointestinal disorder referred to gastroenterologists ( 1 ). Although it has evolved over the years in terms of nomenclature ( 2, 3 ), classifi cation ( 4-6 ), and appreciation of its frequency ( 7 ), a poor understanding of disease pathophysiology has remained a constant. According to the Rome III criteria, a symptom-based classifi cation system, the disease-defi ning symptom profi le encompasses abdominal pain and an altered bowel habit, with distension, bloating, and a variety of disturbances in defecatory function being additional features ( 8 ).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 ). Most recently, the proposal that low-grade infl ammation, 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-infl ammatory cytokines in serum ( 8,(11)(12)(13), has provided a new dimension to this paradigm. The source of this low-grade infl ammation, or immune activation, whether luminal or central, has remained elusive. Polyunsaturated fatty acids (PUFA) and their metabolites have been shown to infl uence infl ammatory processes ( 14 ). Moreover, a pro-infl ammatory PUFA profi le has recently been reported in the maternal separation rodent model, an animal model of IBS ( 15 ).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-infl ammatory profi le 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-infl ammatory profi le in IBS. Plasma AA and related PUFA were quantifi ed 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 identifi es...

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

“…This finding is consistent with data indicating an increase in blood levels of lipid inflammatory mediators such as prostaglandin E2 and leukotriene B4, which are known to be released from newly formed mast cells. 42 The potential activation of the innate gut immune system in IBS could be a sign of previous infection and/or ongoing low-grade inflammation. In this regard, increased faecal levels of the human beta-defensin HBD2, 43 an antimicrobial peptide produced by intestinal epithelial cells, and elevated blood concentrations of the A4-Fla2 and Fla-X bacteria-specific antibodies 44 38,46 Similarly, the Studies identified in PubMed literature search with the following key words:…”

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

“…24 The same strain increased polyunsaturated fatty acids (PUFAs) and exhibited anti-inflammatory effects when coadministered with α-linoleic compared with α-linoleic supplementation alone. 25,26 It is believed that the microbiota, as well as pro-and pre-biotics, can have a significant impact on the gutbrain axis, but further research in this area is needed to reveal the magnitude, mechanisms and clinical relevance of these effects.…”

Osteopathic manipulative treatment and nutrition: An alternative approach to the irritable bowel syndrome

“…mast cells and pro-inflammatory polyunsatured fatty acid metabolites were increased [9][10][11]. Other potential causes of IBS are diet and enteric flora abnormalities leading to low-grade inflammation/immune activation [12].…”