Homo.symbiosus · Assessing, preserving and restoring man-microbes symbiosis

The microbiomics revolution has favoured the recognition of the gut as a true organ and the importance of man-microbes symbiosis in health and disease. Derived from a long co-evolution the latter has been challenged by numerous environmental triggers, modern lifestyles, changes in birth modalities, nutritional transition and therapeutic attitudes. A large fraction of the human population has tentatively entered a man-microbes dysbiotic state characterized by altered interactions between microbiome and host features with auto-aggravating crosstalk signals. The result is increased incidence of incurable immune-mediated diseases of modern societies that affect a third the human population on earth today and for which current therapeutics only address symptoms alleviation, rather than considering man as a holobiont.In this context and its resulting threat for the human species, I will carry out a project geared to open a new era of individualized preventive care and novel gut ecology-based therapeutic approaches. The project will assemble insights and contributions from theoretical to experimental ecology, quantitative and functional microbiomics, preclinical work, cohort studies and clinical trials, so as to:•Validate the concept of critical transition and alternative stable state as it applies to a shift from man-microbes symbiosis to disease-prone man-microbes dysbiosis •Assess the potential of diet alone to promote such a shift •Model the symbiosis-to-dysbiosis transitions and derive predictors of tipping points •Propose counter-measures that may allow to break vicious circles and restore a balanced, health-prone, man-microbes symbiosis by concomitantly acting upon microbiome and host features•Validate strategies to reinforce ecological robustness and restore man-microbes symbiosis Based on a paradigm shift, the proposed work will set the grounds for future personalized preventive nutrition and clinical management considering man as a true holobiont.