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Food phytochemicals are increasingly considered to play a key role in the cardiometabolic health effects of plant foods. However, the heterogeneity in responsiveness to their intake frequently observed in clinical trials can hinder the beneficial effects of these compounds in specific subpopulations. A range of factors, including genetic background, gut microbiota, age, sex and health status, could be involved in these interindividual variations; however, the current knowledge is limited and fragmented. The European network, European Cooperation in Science and Technology (COST)-POSITIVe, has analysed, in a systematic way, existing knowledge with the aim to better understand the factors responsible for the interindividual variation in response to the consumption of the major families of plant food bioactives, regarding their bioavailability and bioefficacy. If differences in bioavailability, likely reflecting differences in human subjects’ genetics or in gut microbiota composition and functionality, are believed to underpin much of the interindividual variability, the key molecular determinants or microbial species remain to be identified. The systematic analysis of published studies conducted to assess the interindividual variation in biomarkers of cardiometabolic risk suggested some factors (such as adiposity and health status) as involved in between-subject variation. However, the contribution of these factors is not demonstrated consistently across the different compounds and biological outcomes and would deserve further investigations. The findings of the network clearly highlight that the human subjects’ intervention studies published so far are not adequate to investigate the relevant determinants of the absorption/metabolism and biological responsiveness. They also emphasise the need for a new generation of intervention studies designed to capture this interindividual variation.
Previous studies have reported the anti-inflammatory properties of pomegranate extracts, suggesting that ellagitannins (ET) and ellagic acid (EA) are the main anti-inflammatory compounds. However, both ET and EA are metabolised in vivo by the gut microbiota to yield urolithins (Uro) which can be found in the gut and in systemic bloodstream. The present study was carried out to evaluate the individual effect of EA and their microbiota-derived metabolites Uro on colon fibroblasts upon IL-1β treatment as an in vitro inflammation model. Uro-A and Uro-B (10 μm) inhibited PGE2 production (85 and 40 %, respectively) after IL-1β stimulation, whereas EA did not show any effect. Uro-A, but not Uro-B, down-regulated cyclo-oxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) mRNA expression and protein levels. Both Uro inhibited NF-κB translocation to nucleus. Slight but significant effects were found in the activation of mitogen-activated protein kinase (MAPK) pathways. Uro-A lowered c-Jun N-terminal kinase phosphorylation state, and both Uro inhibited p38 activation. No metabolites derived from Uro or EA were found in the cell media upon incubation of EA or Uro with the cells, and only traces of the compounds were found inside the cells. The present results suggest that Uro, mainly Uro-A, are the main compounds that are responsible for the pomegranate anti-inflammatory properties. The mechanism of action implicated seems to be via the inhibition of activation of NF-κB and MAPK, down-regulation of COX-2 and mPGES-1 expressions, and consequently,via the reduction of PGE2 production. Taking into account that Uro did not enter the cells, a competitive binding for IL-1β membrane receptor cannot be discarded.
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