Development of a rodent model with an aged human microbiota to test individualized interventional strategies during aging.

Dominique Dardevet  Isabelle Savary-Auzeloux  (Team Improving)

Partners: Jean-Marc Chatel, Claire Cherbuy ( Micalis, jouy en josas), Mathieu Almeida (-Metagenopolis)  

The population aged 60 and over has doubled since 1980 and is expected to reach two billion by 2050. This growth is noticeable not only in developed countries but also in emerging countries. Unfortunately, this increase in longevity does not necessarily mean so-called "successful aging" and there is currently an explosion of chronic noncommunicable diseases (cardiovascular diseases, diabetes, chronic inflammation, cancer ...) which will represent the main causes of co-infection. morbidity, morbidity and mortality in the next few years among the elderly. As a result, the lengthening of this lifespan may be associated with an impaired quality of life, frailty, dependency, and the institutionalization of seniors with an ever increasing public health cost.

Studies in humans have shown that the composition and functions of the gut microbiota play a central role in many pathologies. These evolve with old age. These changes of intestinal microbiota or dysbiosis appear all the more marked that the subjects are in a fragile state of health. Studies show a strong correlation in the elderly between health status and microbiota profile.

Recently, studies of murine microbiota transfer in rodent models have clearly identified that these age-related dysbiosis may play a decisive role in age-related pathologies or complications: thus, it has been shown that the transfer of a microbiota from elderly mice to axenic mice is accompanied, in recipient mice, by changes mimicking characteristics of an elderly organism: increased intestinal permeability, establishment of systemic inflammation and dysfunction of immune cells.

Many nutritional or pharmacological strategies are encouraged to fight or slow down the physiological decline in the broad sense of age. Because of these alterations observed at the level of the microbiota, innovative strategies taking into account the microbiota must now be considered. To achieve effective selection of strategies targeting older people, the use of experimental models is central. The mouse or the rat are the main pre-clinical models, but the microbiota of rodents is very different from that of humans. In order to overcome this problem, our project consists of developing and validating a mouse model of a human microbiota rodent, thus allowing this primordial factor to be taken into account. We will implant a microbiota of healthy or frail elderly people into rodents without germs. We will compare the effect of this transplantation on the physiology of the host with mice in which we have implanted a healthy adult microbiota. Then we will test the "fragility" introduced by the human microbiota of elderly people by an infectious challenge. We will develop a preclinical model that is useful to both the scientific community and industrial partners between the conventional flora rodent model and the human clinical trial.