Preventive and therapeutic effects of dietary omega3 fatty acid-originated 17,18-epoxyeicostetraenoic acid on the control of intestinal allergy

Omega-3 polyunsaturated fatty acids (PUFAs) have anti-allergic properties, but the metabolic progression from dietary oil to host immune system remains to be elucidated. Here we show that 17, 18-epoxyeicosatetraenoic acid (17,18-EpETE) as an anti-allergy metabolite generated in the colon preferentially from dietary omega-3 alpha-linolenic acid (ALA). Incidence of allergic diarrhea was decreased in mice fed with ALA-rich linseed oil (Lin-mice) when compared with mice fed with conventional soybean oil. MALDI-IMS-based imaging analyses revealed increase of ALA and its metabolites, especially eicosapentaenoic acid (EPA), in the colon of Lin-mice. Further, LC-MS/MS-based mediator lipidomics identified the increase of EPA-derived metabolites including 17,18-EpETE in the colon of Lin-mice. Administration of synthetic 17,18-EpETE showed preventive and therapeutic effects on the development of allergic diarrhea. These data suggest that metabolizing dietary w3 PUFAs generates 17, 18-EpETE, which is an endogenous anti-allergic metabolite and potentially is a therapeutic agent to control intestinal allergic diseases.