Diet x gut microbiome-based metabotypes to determine cardio-metabolic risk and tailor intervention strategies for improved health
|Partner Organization||Partner Country|
|University of Barcelona||Spain|
|Federico II University||Italy|
1. Overall project description
The human gut microbiota has been linked with incidence and progression of noncommunicable diseases and their risk factors. Moreover, diet has been identified as an important modulator of microbiota composition and function, but responses vary between individuals. Underlying mechanisms of diet x microbiota interactions remain to be elucidated to provide a foundation for tailored dietary strategies for personalized precision nutrition.
The overall aim of DiGuMet is to explore in depth how gut microbiota interacts with diet and the role of such interactions for disease risk factors in humans. Our aim is to dissect the underlying mechanisms through extensive molecular phenotyping using metagenomics and metabolomics combined with lifestyle data from an established cohort and a dietary intervention study. From the amassed evidence of the role of gut microbiota on metabolic phenotype (metabotype), we hypothesize that: (i) gut microbiota x diet interactions are a major determinant of specific metabotypes that arelinked with cardiometabolic disease risk; and (ii) distinct metabotypes can be identified in free-living subjects based on comprehensive assessment of health-related status, traditional blood-based biomarkers and multi-OMICs; and (iii) these metabotypes could be used as the basis for tailored dietary interventions to maximize health benefits for groups of individuals.
To adress hypotheses i-ii, we have conducted a validation study (n>500) which is a sub-cohort of the Danish Diet, Cancer and Health- Next Generations cohort (DCH-NG; n=45 000; PI Anne Tjønneland) where we conducted repeated sampling at 0, 6 and 12 months across gender, age and fasting strata with the aim to explore wherther we can group individuals into different metabotypes based on the data collected and explore if we can find metabolomics biomarkers of such metabotypes. The data collection was finalized in February 2019. Metabolomics analysis and gut microbiota analysis is currently in progress.
In parallell, we are preparing for a dietary intervention study to test the hypothesis that individuals with signs of metabolic syndrome can be grouped into different metabotypes, determined mainly by their gut microbiota at base-line and if such metabotypes will respond differently when provided a diet rich in fermentable vs non-fermentable cereal fibre. Individuals will be screened and metabotyped and a cross-over design across 2 disctinct metabotypes reflecting differences in gut microbiota will be conducted wiht cardiometabolic risk factors as main outcomes.Specific foods will be provided by industrial collaborator.
We expect that our project will provide insights into new approaches to group individuals according to their molecular phenotype (metabotype) and come up with new strategies for how to improve health through tailoring specific diet for such groups. The concepts and implications have been presented in an opinion paper submitted for publication in July 2019.
DiGuMet project has mainly been in the data collection phase and results from analyses are expected to emerge during late 2019.
* Based on initial work by us and from reports in the literature, we concluded on metabotyping in a recent opinion paper submitted in July 2019:
Metabotyping is a relative new concept within the area of personalized nutrition. In the current literature, metabotypes are often defined either based on clinical and anthropometric markers (disease-associated metabotypes) or the metabolism of certain nutrients and dietary components such as dietary fibre and polyphenols (diet-associated metabotypes). We hypothesize that the disease-associated metabotypes, i.e. metabotypes present in populations at high risk for cardiometabolic diseases, will affect the response to specific diet. We further hypothesize that the gut microbiota is a key determinant and a modifier of metabotypes in addition to habitual diet, genotype, anthropometric measures and biochemical and clinical markers. In other words, the interaction between the host and exogenous exposures (e.g., diet, drugs and gut microbiota) is important for dietary response and identifying such “functional” metabotypes may offer advantages over “clinical biomarker-based” metabotypes and enterotypes for the optimization of the diet to an individual for prevention of cardiometabolic disease. However, much more work is needed to investigate whether responses to particular diets and dietary items are indeed metabotype-specific and whether diet tailored for metabotypes could lead to health improvements that are clinically meaningful. Ongoing and future studies will hopefully shed light on whether metabotype clusters can be deduced in general populations and elucidate their main determinants as well as test whether the response to specific dietary interventions, such as high fermentable fibre diet, will vary across distinct metabotypes. If so, finding easily measured biomarkers of metabotypes is of highest priority to allow tailoring of diet for optimal prevention at large scale.
* During 2019, we finalized recruitment and collection of data for the MAX-study. This study is a validation study including > 500 Danish men and women. Fecal samples, blood samples, antropometric data and detailed food intake data has been collected at base-line and after 6 and 12 months. Metabolomics analsysis of blood and fecal samples and analysis of gut microbiota in fecal samples are now ongoing. This dataset will be used to discover metabolites of indivuduals belonging to different metabotypes (molecular phenotypes).
4.1 List of publications
|Authors||Title||Year, Issue, PP||Doi|
|Stefano Bernardi, Cristian Del Bo, Mirko Marino, Giorgio Gargari, Antonio Cherubini, Cristina Andrés-Lacueeva***, Nicole Hidalgo-Liberona, Gregorio Peron, Raúl González-Dominguez, Paul Kroon, Benjamin Kirkup, Marisa Porrini, Simone Guglielmetti and Patrizia Riso||Polyphenols and Intestinal Permeability: Rationale and Future Perspectives||doi.org/10.1021/acs.jafc.9b02283|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
|Academia||Marie Palmnäs, Carl Brunius, Magali Palau- Rodriguez, Jens Nielsen, Cristina Andres- Lacueva, Gabriele Riccardi, Anne Tjønneland and Rikard Landberg (All project partners/collaborators), DIET X GUT MICROBIOME-BASED METABOTYPES- Determining cardio-metabolic risk and tailoring nutrition for improved health, Nordic Metabolomics Society Annual Meeting, Örebro, August 26-28 2018||ECS Poster presentation about the project and metabotyping concept|
|Academia, Industry, NGO||R Landberg (Coordinator), Personalized nutrition vs Global Recommendations, Whole Grain Summit, 13-15 of November, 2017, Vienna||Oral invited talk. The project was described in the talk|
|Academia, ECS||Marie Palmnäs, Carl Brunius, Magali Palau- Rodriguez, Jens Nielsen, Cristina Andres- Lacueva, Gabriele Riccardi, Anne Tjønneland and Rikard Landberg (All project partners/collaborators), Metabotypes Determining Cardiometabolic Risk and Personalized Diet Strategies to Improve Health, NuGO-conference, Newcastle upon Tyne,3-6 Sept, 2018||ECS talk|
|Members of the Swedish Royal Academy of Engineering Sciences (industrial CEOs, Researchers, etc.)||R Landberg (Coordinator), Precision nutrition- A paradigm for improved health?, Future of Food Seminar, The Academy headquarter, 18 of September, 2018||Invited talk|
|COST-action members, Academia, Industry and NGOs||R Landberg (coordinator) New personalized strategies for optimal metabolic responses to fibre-rich foods, COST-action Positve final conference in Lisbon, 25-26th of September, 2018||Invited talk|
|The Royal Swedish Academy of Agriculture and Forestry||R Landberg (coordinator), Resarch that leads to innovations- the researchers' prespective||Invited talk to a seminar under the title: What foods will we get?|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|