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|
|Danish Cancer Society||Denmark|
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 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 as well as a dietary intervention study. We hypothesize that: (i) gut microbiota x diet interactions are a major determinant of specific metabotypes that are linked with cardiometabolic disease risk; (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 address hypotheses i-ii, we have conducted a validation study, MAX, (n ~500) which is a sub-cohort of the Danish Diet, Cancer and Health- Next Generations cohort (DCH-NG; n=45 000) where samples were collected at 0, 6 and 12 months across gender, age and fasting strata with the aim to explore whether 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 and gut microbiota analyses are currently in progress.
In parallel, we are preparing for a dietary intervention study to evaluate if individuals with signs of metabolic syndrome belonging to two different enterotypes will have differential responses to fermentable or non-fermentable cereal fibre. Individuals will be screened and enterotyped based on the high vs low presence of Prevotella. Participants will then undergo a 6 week cross-over intervention with fermentable- vs nonfermentable fiber and differential effects across enterotypes will be compared. Three fermentable fiber products and matched control products will be provided by industrial collaborators. Cardiometabolic risk factors are the primary outcomes and effects on the metabolome and gut microbiome will also be evaluated.
We expect that our project will i) provide insight into diet x microbiota interactions; ii) provide novel methods for grouping individuals according to their metabotype based on multiomics data; and iii) propose tailoring diet to distinct enterotypes as a novel disease prevention strategy. The concepts and implications have been presented in an opinion paper published November 2019.
The DiGuMet project has mainly been in the experimental analysis and data preparation phase (MAX study) and been preparing for the dietary intervention. The data analysis is expected to start spring 2020 and the intervention recruitment was planned for spring 2020.
*The DiGuMet consortium wrote a perspectives article on metabotyping and group-based dietary advice for precision nutrition and prevention of cardiometabolic disease. The article was published in November 2019 in the journal Advances in Nutrition and highlighted by the American Society of Nutrition on their blog in January 2020.
*The MAX validation study of the DCG-NG cohort was concluded in February 2019. Plasma samples for the ~500 Danish participants have been analyzed with untargeted and targeted metabolomics at all three time points (baseline, 6 and 12 months). The data collected on diet, clinical and anthropometric variables, disease status, medication, physical activity and socioeconomic factors is being prepared for statistical analysis and is expected to be ready starting spring 2020.
*The UHPLC-MS metabolomics platform has been expanded and can at present identify and quantify about 1000 metabolites commonly found in biological samples such as urine, serum and plasma. These include about 500 endogenous metabolites, 450 food-derived metabolites, 50 common pollutants, 50 drugs as well as microbiota-derived metabolites and biomarkers related to lifestyle habits e.g., smoking and alcohol consumption. This comprehensive method provides excellent opportunities to detect diet, gut microbiota and disease related biomarkers in the MAX study and beyond.
*We have set up and evaluated a protocol for freeze-drying fecal samples for the subsequent analysis of both gut microbiota and fecal metabolites. The protocol and the metabolomics results were published in the journal Metabolomics in April 2020.
*A new screening and stratification strategy has been set up for the intervention study to identify individuals with low or high Prevotella enterotypes. Food products rich in either fermentable fiber or nonfermentable fiber (control) will be produced specifically for the intervention. A study protocol for the intervention has been drafted.
* The DiGuMet project has started a collaboration with Carbiotix (https://carbiotix.com/) as a SME to provide a specific fermentable fiber fraction for the dietary intervention study.
*The DiGuMet project has been expanded to develop and use a method to estimate the intake of dietary polyphenolic compounds in the MAX study and in the large DCH-NG cohort. Researchers from Spain and Denmark have been in close collaboration to link an in-house database (Barcelona) to the comprehensive dietary data collected by the Danish partner. The amount of polyphenols consumed for each individual and day (mg/day) will be estimated from the 1670 food items and >5000 ingredients from the 24h dietary recall and the 475 food items and >1200 ingredients from the food frequency questionnaire. This data is expected to be ready summer 2020.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Doi|
|Spanish Partner: 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||2019||doi.org/10.1021/acs.jafc.9b02283|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
|The Royal Swedish Academy of Agriculture and Forestry||Swedish partner: R Landberg (coordinator), Research that leads to innovations- the researchers' perspective||Invited talk to a seminar under the title: What foods will we get?|
|Academia, Biomarker validation and identification of metabotypes for personalized nutrition in the Diet, Cancer and Health – Next Generations cohort,||Danish and Swedish Partner: Agnetha Rostgaard-Hansen, Jytte Halkjær, Anne Tjønneland, Marie Palmnäs, Carl Brunius, Rikard Landberg, Biomarker validation and identification of metabotypes for personalized nutrition in the Diet, Cancer and Health – Next Generations cohort, Biomarker validation and identification of metabotypes for personalized nutrition in the Diet, Cancer and Health – Next Generations cohort Meeting name and place: Nordic Metabolomics Society workshop and Throne Holst symposium, Oslo, Norway, October 31st 2019||Poster presentation|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|