During the past decade, there has been increasing interest the relationship between gut microbes and human health. Multiple studies have demonstrated links between these microbiota and cardiometabolic disorders — which include obesity, metabolic syndrome, diabetes, and cardiovascular diseases. These non-communicable diseases (NCDs) are a tremendous burden on European populations and health systems: the cost of cardiovascular diseases alone to the European economy is currently estimated at €192 billion per year and the cost of obesity is 89 billion euros annually.
We are pleased to interview Professor Karine Clément, who leads the important multinational, multidisciplinary project MetaCardis. This major multi-year EU-funded research project investigates the role of gut microbes in cardiometabolic diseases (CMDs), including obesity. The main investigatory approach is metagenomics and the use of clinical and experimental studies. Professor Clement, thank you for speaking with us about the project.
Please tell us about the motivation and inspiration for developing MetaCardis.
With multiple studies from the past decade showing links between the gut microbiota and cardiometabolic disorders—which include obesity, metabolic syndrome, diabetes, and cardiovascular diseases— as a group of European investigators from different field, we initially saw a major opportunity to develop new approaches to treatment and move toward precision medicine for individuals with these conditions. These obesity-related disorders are heterogeneous by nature. The idea was that MetaCardisproject could lay the groundwork for progressing toward precision medicine by finding physiological pathways that might lead to new therapies, and by discovering gut microbial factors including metabolites that contribute to the progression of these diseases—but most importantly, the project could help medical researchers learn how to refine the existing diagnostic categories based on new measures (that is, targets or pathways), eventually allowing subsets of patients to be funnelled toward therapies that will work more reliably. Thus the project brings together physicians and researchers in fields ranging from obesity, diabetes, and cardiology to microbiology, immunology, molecular biology, physiology, and bioinformatics, actually 15 research institutions in six European countries, to address these challenging objectives.
Thank you. Can you define metagenomics for us? Please outline the project for our readers.
Metagenomics refers the study of the metagenome and the metagenome is the collective genome of microorganisms in a given environment. In the case of metacardis we explore the metagenome of bacteria located in the gut by direct sequencing to DNA stools (called Shotgun metagenomics). The overall idea is to provide information on the microbial richness, diversity, as well as bacterial groups associated with stage of progression of cardiometabolic disorders. There has been several steps. First to work on historical cohorts to identifye groups of bacteria potentially linked with clinical components of cardiometabolic diseases.
In the mean time, combined efforts of clinical investigators have resulted in the successful recruitment of over 2000 patients from three European centres (in Paris, France, Copenhagen Denmark, and leipsig Germany). The subjects fall into nine clinically defined groups related to cardiovascular and metabolic diseases: Metabolic syndrome, obesity, obesity, undergoing bariatric surgery, diabetes, acute coronary artery disease, and chronic coronary artery disease without heart failure and with heart failure, and healthy controls. In this new cohort, we have now gathered information regarding 1400 patient-related clinical and lifestyle variables, along with stool metagenomics and metabolomics data from serum and urine. So in addition to the standard information about subject age and anthropometric characteristics (waist circumference, BMI, body composition with percentage body fat), we measured clinical and biological characteristics (cholesterol, blood pressure, fasting blood glucose, inflammatory markers) and lifestyle factors related to medication use and history, physical activity, and dietary/nutrient intake. All these factors can impact on the shaping of the gut microbiota. Among many objectives, we are currently asking i) what are factors related to lifestyle/sociodemographic factors, patient physiology, or microbiota associated with different stages of cardiometabolic diseases? ii) How do these factors combine to constitute a healthy phenotype? iii) Are certain gut microorganisms or metabolites responsible for the onset or progression of cardiometabolic diseases? Do certain gut biomarkers flag cardiovascular complications arising from obesity and diabetes?
The MetaCardis project team has published an impressive group of high quality papers in peer reviewed journals since 2013.
Indeed, the Metacardis research groups have been really productive during these past 5 years, with 67 international publication citing the Metacardis consortium and can be found on the Metacardis website. New gut-microbiota based hypotheses in obesity and metabolic disorders have been produced as well as methodological approaches. But this investigatory phase is not over because the groups with mutidisciplinary expertise are currently exploring in depth the new Metacardis cohort as mentioned above. We are now at the heart of the study in its initial objective and we hope we can produce new data in the near future.
Consortium Partners include the Institute of Cardiometabolism and Nutrition in Paris (ICAN), the Integrated Research and Treatment Center Adiposity Diseases in Leipzig (IFB) and the Novo Nordisk Foundation Center for Basic Metabolic Research (NNFCBMR) in Copenhagen; INRA, Imperial College London,University of Copenhagen,University of Gothenburg, VIB, EMBL, The Public Assistance Hospital of Paris, Danone Research, BioByte, Chalmers University of Technology, and Cargill.