Polyunsaturated fatty acids, specialized pro-resolving mediators, and targeting inflammation resolution in the age of precision nutrition.

Abstract Chronic inflammation contributes toward the pathogenesis of numerous diseases including, but not limited to, obesity, autoimmunity, cardiovascular diseases, and cancers. The discovery of specialized pro-resolving mediators (SPMs), which are critical for resolving inflammation, has commenced investigation into targeting pathways of inflammation resolution to improve physiological outcomes. SPMs are predominately synthesized from the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Therefore, one viable strategy to promote inflammation resolution would be to increase dietary intake of EPA/DHA, which are deficient in select populations. However, there are inconsistencies between the use of EPA/DHA as dietary or pharmacological supplements and improved inflammatory status. Herein, we review the literature on the relationship between the high n-6/n-3 PUFA ratio, downstream SPM biosynthesis, and inflammatory endpoints. We highlight key studies that have investigated how dietary intake of EPA/DHA increase tissue SPMs and their effects on inflammation. We also discuss the biochemical pathways by which EPA/DHA drive SPM biosynthesis and underscore mechanistic gaps in knowledge about these pathways which include a neglect for host genetics/ethnic differences in SPM metabolism, sexual dimorphism in SPM levels, and potential competition from select dietary n-6 PUFAs for enzymes of SPM synthesis. Altogether, establishing how dietary PUFAs control SPM biosynthesis in a genetic- and sex-dependent manner will drive new precision nutrition studies with EPA/DHA to prevent chronic inflammation in select populations.