The Milieu Intérieur project is an ambitious population-based study coordinated by the Institut Pasteur, Paris. The objective is to dissecte the interplay between genetics and environment and their impact on the immune system.
This project is named after the French physiologist Claude Bernard’s concept of milieu intérieur and aims to establish the determinants of a healthy immune response by identifying genetic and environmental factors that contribute to the observed heterogeneity of immune responses. Restoring the ‘personal’ in medical care is a major challenge for medicine, and the driving vision of the project. This project is coordinated by Pr Matthew Albert and Dr Lluis Quintana-Murci and is part of a larger French Governmental Initiative called Investissement d'Avenir - Laboratoire d’Excellence (LabEx).
The objectives of the Milieu Intérieur project are to:
- Establish a deep understanding of immune variance;
- Define how immune phenotypic variation is genetically controlled and;
- Ascertain the role of the microbiota in regulating immune programs.
These efforts will establish parameters for stratifying individuals within a population, thus making it possible to glean meaningful interpretation from measurements of stress-induced host response. In achieving this goal, the project will provide a foundation for defining perturbations in an individual’s immune responses, thus laying the foundation for personalized medicine.
One innovative aspect of the project relies on the use of a whole-blood assay device - TruCulture® - which preserves physiological cellular interactions and provides a reproducible means of assessing the complexities of innate and adaptive human immune responses.
A total of 32 different immune stimuli conditions have been selected and whole blood assays have been validated, standardized and produced.
In order to realize the promise of personalized medicine, one pending challenge is to establish the boundaries of a healthy immune response, and to correlate this information with human genome variation and environmental factors.
To that end, the Milieu Intérieur Consortium initiated in September 2012 a 1,000 person population-based study in order to assess the determinants of immunologic variance within the general healthy population "Genetic & Environmental Determinants Of Immune Phenotype variance: Establishing A Path Towards Personalized Medicine (ID-RCB Number: 2012-A00238-35)". A de novo study-group of 1,000 healthy individuals (1:1 sex ratio) stratified across five-decades of life (age 20 – 70) from French-descent and recruited as per a detailed medical questionnaire has been recruited between September 2012 and August 2013. Whole blood was collected for immunologic phenotyping, functional immune stimulation and preparation of DNA for genomic analysis. Fecal samples and nasal swabs were obtained for metagenomic studies. Punch biopsies of the skin were taken and primary fibroblast lines were generated for future mechanistic investigation.