In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega‐3 and omega‐6 long chain polyunsaturated fatty acids (LC‐PUFAs), notably EPA (eicosapentaenoic acid, 20:5n‐3), DHA (docosahexaenoic acid, 22:6n‐3), and ARA (arachidonic acid, 20:4n‐6), and their transformation into bioactive lipid mediators. In this sense, new families of PUFA‐derived lipid mediators, including resolvins derived from EPA and DHA, and protectins and maresins derived from DHA, are being increasingly investigated because of their active role in the “return to homeostasis” process and resolution of inflammation. Recent findings reviewed in the present study highlight that the omega‐6 fatty acid ARA appears increased, and omega‐3 EPA and DHA decreased in most cancer tissues compared to normal ones, and that increments in omega‐3 LC‐PUFAs consumption and an omega‐6/omega‐3 ratio of 2–4:1, are associated with a reduced risk of breast, prostate, colon and renal cancers. Along with their lipid‐lowering properties, omega‐3 LC‐PUFAs also exert cardioprotective functions, such as reducing platelet aggregation and inflammation, and controlling the presence of DHA in our body, especially in our liver and brain, which is crucial for optimal brain functionality. Considering that DHA is the principal omega‐3 FA in cortical gray matter, the importance of DHA intake and its derived lipid mediators have been recently reported in patients with major depressive and bipolar disorders, Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. The present study reviews the relationships between major diseases occurring today in the Western world and LC‐PUFAs. More specifically this review focuses on the dietary omega‐3 LC‐PUFAs and the omega‐6/omega‐3 balance, in a wide range of inflammation disorders, including autoimmune diseases. This review suggests that the current recommendations of consumption and/or supplementation of omega‐3 FAs are specific to particular groups of age and physiological status, and still need more fine tuning for overall human health and well being.

MetaboLights is a global database for metabolomics studies including the raw experimental data and the associated metadata. The database is cross-species and cross-technique and covers metabolite structures and their reference spectra as well as their biological roles and locations where available. MetaboLights is the recommended metabolomics repository for a number of leading journals and ELIXIR, the European infrastructure for life science information. In this article, we describe the continued growth and diversity of submissions and the significant developments in recent years. In particular, we highlight MetaboLights Labs, our new Galaxy Project instance with repository-scale standardized workflows, and how data public on MetaboLights are being reused by the community. Metabolomics resources and data are available under the EMBL-EBI’s Terms of Use at https://www.ebi.ac.uk/metabolights and under Apache 2.0 at https://github.com/EBI-Metabolights.

Apolipoprotein E ( APOE ) genotype is the strongest prevalent genetic risk factor for Alzheimer's disease (AD). Numerous studies have provided insights into the pathologic mechanisms. However, a comprehensive understanding of the impact of APOE genotype on microflora speciation and metabolism is completely lacking. In this study, we investigated the association between APOE genotype and the gut microbiome composition in human and APOE–targeted replacement (TR) transgenic mice. Fecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity in group‐aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate‐producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gut microbiota of APOE ‐TR mice. Furthermore, metabolomic analysis of murine fecal water detected significant differences in microbe‐associated amino acids and short‐chain fatty acids between APOE genotypes. Together, these findings indicate that APOE genotype is associated with specific gut microbiome profiles in both humans and APOE ‐TR mice. This suggests that the gut microbiome is worth further investigation as a potential target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention of AD.—Tran, T. T. T., Corsini, S., Kellingray, L., Hegarty, C., Le Gall, G., Narbad, A., Müller, M., Tejera, N., O'Toole, P. W., Minihane, A.‐M., Vauzour, D . APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology. FASEB J. 33, 8221–8231 (2019). www.fasebj.org

The efficacy of the diphenol curcumin as a cancer chemopreventive agent is limited by its chemical and metabolic instability. Non-enzymatic degradation has been described to yield vanillin, ferulic acid, and feruloylmethane through cleavage of the heptadienone chain connecting the phenolic rings. Here we provide evidence for an alternative mechanism, resulting in autoxidative cyclization of the heptadienone moiety as a major pathway of degradation. Autoxidative transformation of curcumin was pH-dependent with the highest rate at pH 8 (2.2 μm/min) and associated with stoichiometric uptake of O₂. Oxidation was also catalyzed by recombinant cyclooxygenase-2 (COX-2) (50 nm; 7.5 μm/min), and the rate was increased ≈10-fold by the addition of 300 μm H₂O₂. The COX-2 catalyzed transformation was inhibited by acetaminophen but not indomethacin, suggesting catalysis occurred by the peroxidase activity. We propose a mechanism of enzymatic or autoxidative hydrogen abstraction from a phenolic hydroxyl to give a quinone methide and a delocalized radical in the heptadienone chain that undergoes 5-exo cyclization and oxygenation. Hydration of the quinone methide (measured by the incorporation of O-18 from H₂¹⁸O) and rearrangement under loss of water gives the final dioxygenated bicyclopentadione product. When curcumin was added to RAW264.7 cells, the bicyclopentadione was increased 1.8-fold in cells activated by LPS; vanillin and other putative cleavage products were negligible. Oxidation to a reactive quinone methide is the mechanistic basis of many phenolic anti-cancer drugs. It is possible, therefore, that oxidative transformation of curcumin, a prominent but previously unrecognized reaction, contributes to its cancer chemopreventive activity.