MicrobioTAging

• Overall objective:

Aging is a progressive and cumulative phenomenon accompanied by chronic, low-level inflammation and profound impairment of the adaptive immune system. The latter contributes significantly to tumor development and infectious diseases, leading to increased morbidity and mortality. Furthermore, vaccination efficacy is significantly reduced in the elderly population, limiting preventive prophylaxis.

As part of the MicrobioTAging project, we aim to evaluate the role of intestinal dysbiosis in age-related immune system dysfunction by demonstrating the link between gut microbiota, inflammation, and T cell dysfunction.

• Scientific and societal issues:

Aging of the global population has become the world’s most significant demographic, medical, and social problem. Healthy aging is therefore the Holy Grail of any society. Understanding the parameters that define the boundary between healthy and unhealthy aging is a major challenge that will open the door to finding new preventive or curative treatments to enable older adults to age successfully.

• Project focuses:

The main focuses of the MicrobioTAging project are:

1) Characterize intestinal dysbiosis (taxonomy and metabolome) that develops with age and establish the link between intestinal dysbiosis and immune system aging: Complementary strategies, such as fecal flora transfer, ablation of potentially harmful intestinal bacteria (antibiotics) in older animals, and analysis of simplified microbiota mouse models, will be used.

2) Study the impact of sex hormones and inflammatory cytokines on intestinal dysbiosis that evolves with age: To ensure translational relevance, the correlation between intestinal microbiota, microbial metabolites, inflammatory cytokines, and T cell phenotype in two cohorts of healthy human volunteers aged 50 to 108 years will be established.

3) Identify bacterial strains and microbial metabolites that correlate with inflammation and immune system dysfunction in mice and humans. The candidates (bacteria, metabolites) will then be tested for their ability to accelerate or slow inflammation and T cell aging.

4) Evaluation of the link between age-related dysbiosis and the immune response to influenza or influenza vaccination in the mouse models described above, as well as in cohorts of volunteers.

Taken as a whole, the MicrobioTAging project could provide a better understanding of the influence of age on the immune system and the development of innovative strategies based on manipulating the gut microbiota to improve the immune system’s capacity in older adults.

• MicrobioTAging project presentation video