MASCAREIGNE

• Overall objective:

While the contribution of the human intestinal microbiota to cardiometabolic risks is no longer in doubt, the mediators of these effects remain uncertain, particularly due to numerous confounding factors and insufficient consideration of the diversity of human populations, both genetic and cultural. The MASCAREIGNE project aims to fill these gaps.

• Scientific and societal issues:

The MASCAREIGNE project is based on an integrative study of a representative sample of 1,000 people from the population of La Réunion, an island in the Mascarene Archipelago and a French department with numerous cases of dyslipidemia and a record prevalence of type 2 diabetes.

Using a unique biobank comprising saliva, fecal, and blood samples, combined with abundant metadata (questionnaires, biological and clinical assessments), this project aims to better characterize the microbiota-metabolism relationship and identify potential levers for action on cardiometabolic risks. More specifically, it will test the hypothesis of an effect of different microbiotas (oral, intestinal, and blood) on blood sugar and lipid profiles, via mediators that have yet to be identified.

The project will also assess the effect of inter-individual variability in terms of diet, exposure to infectious agents and human genetics on these mediators. Taking these factors into account is critical in the particular context of La Réunion Island, characterized by great cultural and genetic diversity as well as high pathogenic pressure.

• Project focuses:

The MASCAREIGNE project is structured around seven axes:

Axis 1: Complete the clinical-biological sampling, the first half of which has already been completed, and generate metagenomic data to obtain a high-resolution image of the island’s microbiota: not only the intestinal microbiota, but also the oral and blood microbiota, which represent all possible modalities of interaction with the host’s metabolism.

Axis 2: Study the interactions between microbiota and metabolism. The project aims to identify blood metabolic markers that act as intermediaries, or “mediators,” between microbiota variability, on the one hand, and blood glucose and lipid profiles, on the other.

Axis 3: Assess the influence of the infectious component, based on serological and metagenomic data. More specifically, the aim will be to test whether exposure (past or present) to pathogens prevalent on Reunion Island can have an effect on the mediators of interest.

Axis 4: Analyze the human genomic component, with the objective of determining whether the high genetic variability of the Reunion Island population can have an effect on these mediators. Using complete genomes, the project will notably test the hypothesis of an interaction between adaptive interbreeding and cardiometabolic risks (diabetes and dyslipidemia).

Axis 5: Study the relationships between oral and intestinal microbiotas to assess the degree of permeability between these different compartments.

Axis 6: Combining integrative models and experimental approaches: After identifying the microbiota components most likely to act as effectors of cardiometabolic risks, the project will test the most promising candidates using experimental approaches in preclinical mouse models of diabetes and dyslipidemia.

Axis 7: Dissemination of the work to all audiences, locally, nationally, and internationally (popularization and scientific dissemination)

• MASCAREIGNE project presentation video