Presentation

The objective of the VaRIAe team is to describe, understand, and predict interindividual variability in metabolic and inflammatory responses to diet, with the aim of developing personalized nutritional strategies to promote healthier aging.

Research objective

The VaRIAe team is developing an original approach to investigate interindividual variability in responses to diet. Indeed, studies across multiple health outcomes (weight loss, hypertension, postprandial glycemic and lipemic responses, etc.) have shown that some individuals respond more favorably than others to nutritional interventions. This highlights the potential to improve dietary recommendations by accounting for interindividual differences. These differences involve both metabolic and physiological responses and arise from the complex interaction between intrinsic factors (age, sex, genetics, etc.) and extrinsic factors (diet, microbiota, physical activity, environment).

The loss of metabolic and inflammatory flexibility in midlife represents a key target, as it can be considered an early marker of dysregulation likely to promote the development of cardiometabolic diseases during aging.

Characterizing individual dietary responses and identifying their major determinants will enable the definition of metabotypes, i.e., groups of individuals sharing common characteristics in their response to diet. Complementary analyses will then be conducted to test our hypotheses regarding the physiological and metabolic mechanisms underlying the differences observed between these metabotypes.

The ambition of VaRIAe is to generate knowledge that can be translated into tailored, broadly accessible nutritional strategies, thereby contributing to healthier aging for all.

Our scientific objectives are structured around three main themes:

1. Understanding variability in postprandial metabolic and inflammatory responses

• Identify individual response profiles to foods in terms of glycemic and lipemic responses, in order to elucidate the associated physiological mechanisms and improve prevention of cardiometabolic risk.
• Identify metabotypes at highest risk of impaired muscle protein anabolism.
• Explore variability in inflammatory responses and identify groups at risk of inflammatory dysregulation based on key mediators (oxylipins and cytokines).
• Investigate interactions between high-risk metabotypes and hormonal status in women during the menopausal transition.

2. Exploring variability in the absorption and metabolism of dietary constituents of interest, and its impact on their health effects

• Identify and characterize existing metabotypes for the metabolism of polyphenols of major interest in the prevention of cardiometabolic risk.
• Characterize variability in inflammatory responses to dietary omega-3 fatty acids.

3. Exploring associations between metabolomes and health/aging outcomes

• Precisely characterize individual nutritional exposures through exploration of the food metabolome.
• Describe, understand, and predict the evolution of metabolic phenotypes.

Approaches and Methods

Innovative clinical studies: nutritional intervention studies with inclusive and diverse recruitment, home-based participation, self-collection of samples, and participatory research approaches (RéseautAGE).

Prospective cohorts: collaborations in France (SuViMax, NutriNet-Santé, B’Cube, Milieu Intérieur), Europe (Whitehall, BASE II, Di@bet.ES), and Canada (NuAGE).

Multidimensional phenotyping: assessment of dietary intakes and exposures, metabolic capacities, inflammatory responses, and oral and vascular health, using functional tests, questionnaires, biochemical analyses, and multi-omics approaches.

Integrated investigation of exposures and metabolism through metabolomics.

Mechanistic exploration: use of metabolic tracers, ex vivo inflammatory stimulation, and animal models (rodents and minipigs) of aging and obesity/insulin resistance.