DiGuMet Project: Diet x gut microbiome-based metabotypes to determine cardio-metabolic risk and tailor intervention strategies for improved health

​Diet is a major risk factor for type 2 diabetes and cardiovascular disease. Modifying the diet is therefore an important prevention strategy for metabolic diseases, yet there is accumulating evidence suggesting that different groups of individuals benefit from different types of diet. The gut microbiota plays a crucial role in human metabolism and has recently been shown to determine the health response to diets within an individual. Thus, we hypothesize that the interactions between the gut microbiota and diet will dictate whether a diet results in improvements in disease risk.

We will identify metabotypes and biomarkers by extensive analysis (metabolomics, metagenomics of gut microbiota and lifestyle factors) of 720 adults with cardiovascular disease risk factors. Participants are part of a validation sub-study of the Danish Diet Cancer and Health-Next Generation (DCH-NG) study. Next, we will recruit new participants in Italy that present with these metabotypes to conduct a dietary intervention study evaluating the health response to fermentable and nonfermentable cereal fiber. We will monitor changes in the cardiovascular disease phenotype within each metabotype and intervention group.

Our aim is that our collaborative effort ultimately will provide evidence-based dietary recommendations, directed towards distinct groups of individuals, that will lead to effective and sustainable health improvements preventing cardiovascular disease.

The project is divided into four work packages, described below.

Work Packages

Work Package 1: Gut microbiome x diet interactions -dynamics over time in free-living individuals

​In this Work Package, we aim to identify and characterize major microbiome-associated lifestyle variables, including specific foods and dietary components, through a metagenomic association analysis. The analysis will be performed for 720 men and women (DCH-NG sub-study). We will also assess reproducibility in the gut microbiota composition over 1 year and relate to changes in diet and life-style.

Work package leader: Rikard Landberg (Chalmers University of Technology)

Work Package 2: Identifying metabolite biomarkers for gut microbiota x diet interactions

​Here, we seek to discover plasma, urinary and fecal metabolite biomarkers that reflect gut microbiota diversity and specific associations with food intake in humans (DCH-NG study). Untargeted and targeted LC-MS based metabolomics will be used to identify biomarkers. Findings will be presented as part of a novel and open database for biomarkers.

Work package leader: Cristina Andres-Lacueva (University of Barcelona, Spain)

Work Package 3: Identifying metabotypes and biomarkers by novel data fusion strategies

Schematic of the DiGuMet project showing how tailoring the dietary recommendations to groups of individuals through metabotyping may lead to improved health in adults with high risk of cardiovascular disease.

 

In Work Package 3 we aim to identify metabotypes present in the DCH-NG sub-study, based on phenotypic traits from untargeted and targeted metabolomics, gut microbiota and lifestyle and health parameters. We will apply novel data fusion methodologies to identify the independent and interactive roles of gut microbiota and specific dietary components on cardiometabolic risk factors. LC-MS metabolomics will be used to identify metabolite biomarkers.

Work package leader: Rikard Landberg (Chalmers University of Technology)

Work Package 4: Dietary intervention across gut microbiota-related metabotypes

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Study design of the cross-over dietary intervention evaluating fermentable and nonfermentable fiber in respect to cardiovascular disease and the two metabotypes identified in Work Package 3.

In the final work package, we will conduct 6-week long interventions with diets rich in either fermentable or non-fermentable cereal fiber with 80 subjects presenting with either Metabotype A or B (see Work Package 3). Endpoints include postprandial glucose and insulin, fasting lipids, HbA1c and blood pressure. The intervention will allow us to test the hypothesis that the gut microbial-related metabotypes will determine the health response following the diets. Metabolomics and gut microbial analysis will be used to monitor shifts in the cardiovascular disease phenotype throughout the intervention, as well as to evaluate the differential response for potential responders and non-responders.

Work package leader: Gabriele Riccardi (Frederico II University, Italy)

• Rikard Landberg

  Professor; Head of Division of Food and Nutrition Science

  Rikard Landberg is professor of Food and Health. His group is studying the impact of food and food components may have on health and disease risk in observational and intervention studies as well as...
• Carl Brunius

  Associate professor, Biology and Biological Engineering, Food and Nutrition Science

  Carl Brunius investigates connections between food and health, to develop approaches for precision nutrition, i.e. healthy food tailored for individual requirements. His research focuses on Big Data...
• Marie Palmnäs

  Postdoc

  Marie Palmnäs is the project manager of a European collaboration effort by the DiGuMet Consortium (JPI-INTIMIC). Her research focuses on the interaction between the diet and the gut microbiota. The...

​Universita degli Studi di Napoli Federico II, Italy

	​ ​Anne Tjønneland ​ ​Jytte Halkjær

	Dra. Cristina Andres-Lacueva is Associate Professor at the Nutrition, Food Science & Gastronomy Department of the Pharmacy and Food Science Faculty at the University of Barcelona (UB) and coordinator of the BIOMARKERS AND NUTRITIONAL & FOOD METABOLOMICS research group 2017SGR1566. Coordinator of the UB Biomedical Research Network on Frailty and Healthy Aging (CIBERFES-isciii). My scientific activity is mainly focused in dietary and nutritional assessment as the major determinants of human health. The understanding of qualitative and quantitative links between diet, nutritional phenotype and risk factors for diet-related chronic diseases; and The discovery of proper and predictive biomarkers that characterize the trajectory from health to disease in the context of dietary intake and phenotypic changes. Coordinator of the UB node in competitive projects of the European Community such as Cook2Health, Innovation by Design project and INJOY from the Campus EIT-Health (The European Institute of Innovation and Technology's (EIT) Health-Knowledge and Innovation Community (KIC). Active participation on the EU- Joint Programming Initiative a Healthy Diet for a Healthy Life JPI HDHL; H-index of 56 (web of Science). ORCID 0000-0002-8494-4978; ResearcherID: J-3377-2012 . @Nutrimetabolom
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​	​Dr. Raúl González-Domínguez obtained his PhD degree in Chemistry by the University of Huelva (Spain) in 2015, and then was awarded by the Spanish Ministry of Science with a post-doctoral grant to join the Nutrimetabolomics research group headed by Prof. Cristina Andrés-Lacueva. His main research interests are focused in the development and application of targeted and un-targeted metabolomics approaches in epidemiological, nutritional and biomedical research.
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​	​Dr. Raul Zamora-Ros is graduated in both Nutrition and Food Science and also obtained a master on Statistics and Epidemiology. He earned his PhD in Nutrition from the University of Barcelona in 2008. He did his PostDoc on Nutritional Epidemiology at the Bellvitge Institute for Biomedical Research (IDIBELL; Spain), International Agency for Research on Cancer (IARC-WHO; France) and the University of Cambridge (UK), before joining his current position as principal investigator at the Unit of Nutrition and Cancer (IDIBELL) since February 2016. He is interested in whether dietary factors, particularly polyphenols and polyphenol-rich foods, are causally associated with the development of chronic diseases. He has published over 85 peer-review articles and above 10 book chapters in his area.
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​	​Núria Estanyol-Torres is a Food and Agricultural Technical Engineer from the University of Girona. She has a Master’s degree on Nutrition and Health from the Universitat Oberta de Catalunya and a Master’s degree on Research on Nutrition and Metabolism from the University Rovira i Virgili and the University of Barcelona. She has experience as technician and technical manager on R&D and quality in food industry. At present she is working as a Research Technician and doing her PhD in the Biomedicine Doctoral Programme in "Biomarkers and Nutritional and Food Metabolomics" research group headed by Prof. Cristina Andrés-Lacueva at the University of Barcelona.
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​	​Fabian Lanuza has a degree in Nutrition from Facultad de Medicina, Universidad de La Frontera (UFRO), and a Master degree of Science in Food and Nutrition (Major in Human Nutrition) from Institute of Nutrition and Food Technology, University of Chile. He participated as an assistant researcher in the international project INFORMAS (International Network for Food and Obesity / non-communicable diseases Research, Monitoring and Action Support) and he worked as a professor in the Department of Pediatrics and Child Surgery at the University de La Frontera (2016-2019). He is doing a research in Nutritional Epidemiology, Nutrition and Dietetics, Obesity, Healthy Lifestyles and Clinical Diseases. Currently, Fabian is a PhD student in Food and Nutrition programme in  “Biomarkers and Nutritional & Food Metabolomics” research group in University of Barcelona with a research predoctoral scholarship from CONICYT (Chile). Also, he is an ad honorem professor in UFRO and participates as a member collaborate of ELHOC (Epidemiology of Lifestyle and Health Outcomes in Chile) and EPICYN (Centro en Epidemiología Cardiovascular y Nutricional) group.