Diet-induced Arrangement of the gut Microbiome for improvement of Cardiometabolic health

The gut microbiota, that is, the communities of microorganisms in the human intestine, was recently recognized as an important factor influencing health throughout all stages of life. Obesity and type-2 diabetes have globally reached pandemic-like prevalence and are major risk factors for the development of cardiovascular diseases, in particular coronary artery disease and stroke. These pathologies are referred to as cardiometabolic diseases (CMD), and to effectively tackle them it is crucial to understand interplays between dietary and microbial factors that promote or inhibit transition from early metabolic symptoms to cardiovascular complications. CMD are associated with dysbiotic microbial ecosystems in the gut, or alterations in the composition and function of the microbiota. Diet is a prime influencing factor of both the intestinal milieu and risks for developing CMD, but knowledge about the reciprocal interaction between dietary components and microbial populations is scant. Moreover, although certain gut microbial metabolites have been implicated in the onset of CMD, molecular mechanisms are poorly characterized and causal relationships have yet to be determined. The DINAMIC consortium will bridge the gap by investigating interactions between diet and the gut microbiota, and the potential of modulating these interactions for prevention of metabolic dysfunction and cardiovascular complications in humans. This would enable novel nutritional strategies for prevention of CMD. The work programme is based on a combination of analysis of prospective and genetically well-characterized human cohorts to study associations between diet, the gut microbiome and cardiometabolic health parameters, with a series of targeted nutritional and microbiota intervention studies. The complementary use of large scale and targeted strategies, and explorative and interventional approaches, will deliver insights into nutritional strategies to develop practices for modulation of the intestinal microbiome to promote cardiometabolic health.

To effectively tackle cardiometabolic diseases (CMD) it is crucial to understand interplays between dietary and microbial factors that promote or inhibit transition from early metabolic symptoms to cardiovascular complications. CMD are associated with dysbiotic microbial ecosystems in the gut, that is, alterations in the composition and function of the microbiota. Diet is a prime influencing factor of both the intestinal milieu and risks for developing CMD, but knowledge about the reciprocal interaction between dietary components and microbial populations is scant. The proposal will investigate interactions between diet and the gut microbiota, and the potential of modulating these interactions for prevention of metabolic dysfunction and cardiovascular complications in humans. This would enable novel nutritional strategies for prevention of CMD. The work programme is based on: (i) state-of-the-art prospective and genetically well-characterized human cohorts to gain detailed insight into associations between dietary habits, the gut microbiome and cardiometabolic health parameters; and (ii) targeted nutritional and microbiota interventions to study causal relationships between specific diet-responsive microbial taxa and related metabolites and the development of metabolic syndrome as risk factor for cardiovascular diseases. The work is underpinned by established pipelines for assessment of 16S rRNA gene diversity and composition, as well as state-of-the-art shotgun metagenomics, metabolomics and data integration platforms. Hence, the complementary use of large scale and targeted strategies, explorative and interventional approaches, as well as standardization innovative assessment of the gut microbiota within the DINAMIC consortium will deliver penetrating insights into nutritional strategies to develop and validate practices for modulation of the intestinal microbiome to promote metabolic and cardiovascular health.

The DINAMIC project will bridge the gap between observational studies linking on the one hand altered microbiota composition and function to health, and on the other, mechanistic insights and practical intervention possibilities. The proposal is a unique opportunity to combine transnational experts in epidemiology, clinical intervention, nutrition, microbial ecology, microbiome research, metabolomics and bioinformatics for the sake of diet-driven improvement of health. It joins the cohorts, expertise and facilities necessary to carry out the ambitious project. The Exploitation Strategy will be developed under the guidance of the IP case manager who will manage how results will be used in the future (e.g. further research, or commercial exploitation). The potential beneficiaries from the knowledge and materials produced include the public, industry and SMEs, and policy and decision makers. Communication (both internal & external), dissemination and exploitation of the project's activities, outcomes and products will be addressed at all stages of the project to maximize impact. The ultimate deliverables from the project will be evidence-based microbiota-based nutritional strategies to prevent cardiometabolic diseases. There will be an important teaching and training component to the research program as partners of the consortium will exchange and promote significant and outstanding transfer of knowledge and mutualisation of technological expertise and tools as well as training our future scientists. Importantly, DINAMIC will form the basis for future collaborative research that will exploit the expected novel discoveries on diet-microbiome parameters that influence cardio-metabolic disease.