Periodic Reporting for period 1 - PolyBiota (Polyphenols and Gut Microbiota interaction in Cardiovascular Health)
Berichtszeitraum: 2020-07-16 bis 2022-07-15
An important number of European Public Health Programmes have considered diet (and, in turn, the consumption of plant-derived foodstuff) as one of the cornerstones in the prevention/treatment of cardiovascular diseases (CVDs). In this regard, (Poly)phenols (constituents of plant foods) have been in the spotlight of food scientists´ investigations as the molecules responsible for the benefits (i.e. anticancer and/or anti-inflammatory effects) associated with vegetables consumption. However, the different responses to (poly)phenols consumption depending on the individual, make it difficult to unequivocally correlate (poly)phenols intake and human health. This is the critical issue the PolyBiota project is intended to improve upon, thus contributing to establish proper diets based on individuals’ features (such as the gut microbiota) as strategy towards the prevention of chronic diseases. The underlying premise of PolyBiota invokes the gut microbiota (individual´s fingerprint) as a key element to shed some light to the role of (poly)phenols on human health. The preliminary results from this investigation showed interesting and potentially ground-breaking outcomes. The consumption of a diet enriched with vegetables or (poly)phenols modulated the inflammatory response in animal models, while this effect was less evident when the gut microbiota was imbalanced. Besides, the study of the effects of (poly)phenols in relevant cellular models, under conditions similar to those described in vivo, described the capacity of these molecules to modulate processes linked to angiogenesis. These results highlight the role of the gut microbiota in modulating the role of (poly)phenols, and how both could act in tandem to exert beneficial effects at the cardiovascular level.
The innovative approach of the PolyBiota project combined traditional and cutting-edge techniques to accomplish the main objectives set in this proposal.
Within the work package (WP)1, during a period of two weeks, the animals were fed a polyphenols-enriched diet and the effect on the modulation of that diet on inflammation modulation and blood vessels formation was measured. The experiment was repeated in animals which consumed antibiotic to determine the role of the gut microbiota. The experiments performed involved analysis of immune cellular populations, analysis of eicosanoids, protein expression and microbial metabolism (microbial metabolites formation) using traditional (e.g. western blot and ELISA assays) and state of the art technologies (e.g. flow cytometry and Q-TOF). The results obtained show an attenuation of the biosynthesis of markers linked to inflammation in animals fed diets enriched with natural products (vegetables or (poly)phenols), whereas these effects were absent in antibiotic-treated animals. The faeces obtained (in sterile conditions) from the animals were processed and analysed (WP2) to determine the modulation of the microbial ecology of the animals that consumed a polyphenols-enriched diet. The Illumina analysis was performed in FISABIO (Valencia) and the groups of microorganisms modulated provide invaluable information about the interaction gut microbiota/(poly)phenols. The knowledge of the role of specific groups of microorganisms will be essential in future studies, including faecal transplant investigation. Besides, we also studied the molecular mechanisms by which the polyphenols exert their effects in a relevant endothelial cellular model. The WP3 included the tubulogenesis assay, endothelial cell migration, cell proliferation, metabolism analysis, western blot, immunofluorescence assays, and in sillico analysis. The results of this WP show the role of important receptors (i.e. VEGFR2) as a target of the dietary polyphenols investigated, and its inhibition as a key mechanism of angiogenesis inhibition. The dissemination and diffusion activities performed through the development of the project targeted the scientific community through the publication of peer-reviewed articles, international seminars, collaboration with other European projects (i.e. PhenolAcTwin #951994), workshops and summer schools’ organization, and attending international conferences (Food Bioactives and Health, Parma, Italy). A wider community was also targeted via press release (local and regional newspapers) and radio interviews, as well as through the participation in the Science Week, mentoring Thesis’ Master students, supervising high school students (IDIES project), etc. The website of the PolyBiota project (polybiota.blogspot.com) prepared within this WP, describes in a comprehensive manner all the activities performed, thus facilitating the follow up of the project. Besides, the preparation of a “career development plan” (i.e. training plan) as well as a “management plan” (open access, financial/risk management) were essential to achieve the objectives of the WP5 and WP6.
Within the work package (WP)1, during a period of two weeks, the animals were fed a polyphenols-enriched diet and the effect on the modulation of that diet on inflammation modulation and blood vessels formation was measured. The experiment was repeated in animals which consumed antibiotic to determine the role of the gut microbiota. The experiments performed involved analysis of immune cellular populations, analysis of eicosanoids, protein expression and microbial metabolism (microbial metabolites formation) using traditional (e.g. western blot and ELISA assays) and state of the art technologies (e.g. flow cytometry and Q-TOF). The results obtained show an attenuation of the biosynthesis of markers linked to inflammation in animals fed diets enriched with natural products (vegetables or (poly)phenols), whereas these effects were absent in antibiotic-treated animals. The faeces obtained (in sterile conditions) from the animals were processed and analysed (WP2) to determine the modulation of the microbial ecology of the animals that consumed a polyphenols-enriched diet. The Illumina analysis was performed in FISABIO (Valencia) and the groups of microorganisms modulated provide invaluable information about the interaction gut microbiota/(poly)phenols. The knowledge of the role of specific groups of microorganisms will be essential in future studies, including faecal transplant investigation. Besides, we also studied the molecular mechanisms by which the polyphenols exert their effects in a relevant endothelial cellular model. The WP3 included the tubulogenesis assay, endothelial cell migration, cell proliferation, metabolism analysis, western blot, immunofluorescence assays, and in sillico analysis. The results of this WP show the role of important receptors (i.e. VEGFR2) as a target of the dietary polyphenols investigated, and its inhibition as a key mechanism of angiogenesis inhibition. The dissemination and diffusion activities performed through the development of the project targeted the scientific community through the publication of peer-reviewed articles, international seminars, collaboration with other European projects (i.e. PhenolAcTwin #951994), workshops and summer schools’ organization, and attending international conferences (Food Bioactives and Health, Parma, Italy). A wider community was also targeted via press release (local and regional newspapers) and radio interviews, as well as through the participation in the Science Week, mentoring Thesis’ Master students, supervising high school students (IDIES project), etc. The website of the PolyBiota project (polybiota.blogspot.com) prepared within this WP, describes in a comprehensive manner all the activities performed, thus facilitating the follow up of the project. Besides, the preparation of a “career development plan” (i.e. training plan) as well as a “management plan” (open access, financial/risk management) were essential to achieve the objectives of the WP5 and WP6.
The underlying thesis of PolyBiota is to consider the gut microbiota as mediator of the biological activity of (poly)phenols and their microbial metabolites. This project provides interesting outcomes about the essential role of the interaction between the gut microbiota and the dietary (poly)phenols to understand the beneficial effects related to their consumption. This will undoubtedly broaden our understanding of the (cellular and molecular) mechanisms underlying the benefits associated with the consumption of dietary (poly)phenols. The knowledge generated will also contribute towards well-designed critical trials (key step into the personalized nutrition strategy), and the generation of indispensable knowledge to meet the criteria established by the European Food Safety Authority (EFSA) to obtain a positive opinion about the health claims natural food products. This will have a positive economic impact as, according to the European Commission, the health claims stimulate the food industry to promote the innovation and development of healthier food products (i.e. nutraceuticals and functional foods) with functional benefits, improving their competitiveness. Given the huge burden related to CVDs (€210 billion according to the European Heart Network), the data of this study might have important implications for public health strategies tailored to the gut microbiota via prevention/treatment of these disorders. In this regard, the innovative approach directly relates the Horizon 2020 Work Program (2018-2020) in health, demographic change and wellbeing, promoting effective strategies towards disease prevention. The promising results obtained hitherto clearly go beyond the current state-of-the-art. A testament of this is reflected by the CSIC-funded extension of the PolyBiota project, which will allow generating additional data that will be the basis for an ERC proposal.