Microbiota Controls the Homeostasis of Glial Cells in the Gut Lamina Propria

Abstract

SummaryThe intrinsic neural networks of the gastrointestinal tract are derived from dedicated neural crest progenitors that colonize the gut during embryogenesis and give rise to enteric neurons and glia. Here, we study how an essential subpopulation of enteric glial cells (EGCs) residing within the intestinal mucosa is integrated into the dynamic microenvironment of the alimentary tract. We find that under normal conditions colonization of the lamina propria by glial cells commences during early postnatal stages but reaches steady-state levels after weaning. By employing genetic lineage tracing, we provide evidence that in adult mice the network of mucosal EGCs is continuously renewed by incoming glial cells originating in the plexi of the gut wall. Finally, we demonstrate that both the initial colonization and homeostasis of glial cells in the intestinal mucosa are regulated by the indigenous gut microbiota.

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

“…Moreover, the extensive interaction of enteric neurons and glia with the highly regenerative and remodeling tissues of the gut wall, such as the intestinal epithelium (45) and mucosal vasculature (46), suggest that ENS homeostasis is integrated into the physiology of the organ. It is therefore surprising that most studies on ENS development so far have focused on the role of neural crest cell-intrinsic factors and that little attention has been paid to the formation of enteric neural circuits in the context of gut organogenesis.…”

Microbe-host interactions: Influence of the gut microbiota on the enteric nervous system

“…These studies support the plasticity of the adult ENS, and, furthermore, the selective influence of particular microbes on the ENS in distinct regions of the GI tract. More recently a role for the microbiota in modulating the flow of enteric glial cells from the ENS to the mucosa has been demonstrated in antibiotic treated Sox10::Cre;R26RConfetti mice (Kabouridis et al, 2015). Moreover, GF mice displayed a decrease in mucosal glial cell staining relative to conventional animals which could be restored upon colonisation.…”

Neuro-Immune Networks in Gastrointestinal Disorders

“…In experiments with germ-free mice, one could show that the number of ENS cells was strongly decreased compared to their controls, which resulted in decelerated gut motility [53]. Moreover, mucosal enteric glial cells were dysregulated with attenuated influx into the intestinal mucosa in antibiotics-treated mice compared to control mice [54]. This state could be reversed by reconstitution with microbiota, which reflects the fundamental role of microbiota in the neuronal intestinal composition [54].…”

“…Moreover, mucosal enteric glial cells were dysregulated with attenuated influx into the intestinal mucosa in antibiotics-treated mice compared to control mice [54]. This state could be reversed by reconstitution with microbiota, which reflects the fundamental role of microbiota in the neuronal intestinal composition [54]. Gut microbiota not only act directly on cells within their microenvironment (neuronal, epithelial, and immune cells) but rather on distant organs as well.…”