Effect of the gut environment on the homeostasis and function of the enteric nervous system

The gastrointestinal (GI) tract performs essential functions that maintain health and homeostasis of organisms. A complex set of tissues of distinct embryological origin (such as epithelial cells and the local immune and nervous systems) interact continuously in order to maintain a functional equilibrium and normal physiology which is constantly threatened by multiple and sometimes severe challenges originating within the wall or the lumen of the gut. The enteric nervous system (ENS) is composed of an intricate and complex network of enteric glial cells (EGCs) and neurons localised into different compartments within the intestinal wall. These cells are involved in controlling virtually all aspects of GI function, including intestinal peristalsis. Due to its positioning at the interface between the internal and external milieu of the body, the ENS shares the same intestinal environment with the highly active immune system and the rich and diverse communities of microbiota and therefore is expected to be influenced by immune responses and microbial dynamics. However, the methodology to study these questions and consequently our understanding of neuro-immune-microbe interactions in the mammalian gut is limited. In this thesis, we examined the effects of the intestinal environment, such as microbiota and adaptive immune system on the homeostasis and function of the ENS in adult animals. We have successfully generated a robust technology to isolate and investigate the molecular profile of enteric neurons from the adult gut, in addition to an in vitro system that allows the establishment and maintenance of the adult EGCs. Moreover, by using germ-free (GF) and inflammation mouse models, our experiments demonstrated that subtle changes in the intestinal environment are enough to alter the normal physiology of the ENS. Furthermore, we found that the adaptive immune system is crucial for maintaining the integrity and functional equilibrium of the ENS. Together, our data suggest that the balance between microbiota and adaptive immune system regulates the organisation and homeostasis of the ENS.Open Acces