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

In this study we seek to identify metabolic phenotypes (metabotypes) and unique biomarkers that can guide personalization of dietary interventions for adults at high risk for cardiovascular disease.

Partner organizations

  • Universita degli Studi di Napoli Federico II (Academic, Italy)
  • University of Barcelona (Academic, Spain)
  • Barilla (Private, Italy)
  • Danish Cancer Research Society Center (Research Institute, Denmark)
Start date 01/01/2018
End date 31/12/2021

​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




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)

Funded by

  • Formas (Public, Sweden)


​Schematic of the planned DiGuMet project exploitation and dissemination of results.

Upcoming  and past conferences
Nordic Metabolomics Conference, August 26-28 2018, Örebro, Sweden
Poster presentation by Marie Palmnäs (Project Manager)

Project publications

Published: Wed 06 Jun 2018. Modified: Tue 02 Oct 2018