The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System

Abstract

The gastrointestinal (GI) tract is essential for the absorption of nutrients, induction of mucosal and systemic immune responses, and maintenance of a healthy gut microbiota. Key aspects of gastrointestinal physiology are controlled by the enteric nervous system (ENS), which is composed of neurons and glial cells. The ENS is exposed to and interacts with the outer (microbiota, metabolites, and nutrients) and inner (immune cells and stromal cells) microenvironment of the gut. Although the cellular blueprint of the ENS is mostly in place by birth, the functional maturation of intestinal neural networks is completed within the microenvironment of the postnatal gut, under the influence of gut microbiota and the mucosal immune system. Recent studies have shown the importance of molecular interactions among microbiota, enteric neurons, and immune cells for GI homeostasis. In addition to its role in GI physiology, the ENS has been associated with the pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, raising the possibility that microbiota–ENS interactions could offer a viable strategy for influencing the course of brain diseases. Here, we discuss recent advances on the role of microbiota and the immune system on the development and homeostasis of the ENS, a key relay station along the gut–brain axis.

Gut Microbiota and Host Metabolism: What Relationship

“…Moreover, the intestine of germ-free mice suffers from several defects. Particularly, their gastrointestinal nervous and immune systems are very immature, and accordingly conventionalization partially corrects these defects [17,18]. More importantly, the gut barrier permeability is markedly altered in germ-free mice, which makes their intestine leaky and especially permeable to a variety of compounds, such as inflammatory lipopolysaccharides [19].…”

Neuro-Immune Networks in Gastrointestinal Disorders

“…Intriguingly, recent reports indicate that microbiota, among other things such as metabolism and emotional behavior, also regulate immune response and neuronal networks [51, 52]. 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].…”

Host‐microbe interaction in the gastrointestinal tract

“…Bacterial metabolites, such as short-chain fatty acids (SCFAs) can also stimulate the local sympathetic nervous system directly via neuronal G-protein coupled receptors (GPCR) (Kimura et al, 2011) or indirectly, via intriguing epithelial-neuro-immune cellular networks. For example, SCFA binding to enteroendocrine cells may trigger a signalling pathway involving pseudopods, neurons and glia to alter adjacent immune cell activity and gut motility (Sommer et al, 2015;Obata and Pachnis, 2016).…”