The Pivotal Role of Microbiota in Modulating the Neuronal-Glial-Epithelial Unit

Abstract

The enteric nervous system (ENS) consists of enteric neurons and enteric glial cells (EGCs) and controls the function of the epithelial barrier. Thus, a novel concept of neuronal-glial-epithelial unit in the gut was put forward by analogy with neuronal-glial-endothelial unit in the brain. The environment in the gastrointestinal (GI) tract is complex as it harbours millions of bacteria, which extensively attach with intestinal epithelium. The cross-talk between the neuronal-glial-endothelial unit and microbiota plays a pivotal role in modulating the epithelial barrier's permeability, intestinal development and immune response. And evidence shows dysbiosis is the potent risk factor in the pathologic process of Parkinson's disease (PD) and inflammatory bowel disease (IBD). In this review, we summarize the compelling results in favor of microbiota serving as the key modulator in the neuronal-glial-epithelial unit development and function, with profound effects on intestinal homeostasis.

Keywords: gut; microbiome; neuronal–glial–epithelial unit.

Figure 1

The enteric nervous system.

Figure 2

The function layers of the neuronal–glial–endothelial unit and the organization of tight junctions. Tight junctions are composed of two membrane proteins the Occludin and Claudins, the intracellular protein ZO protein, which are MAGUK family proteins ZO-1, ZO-2, and ZO-3, and the junction adhesion molecule (JAM).

Figure 3

Pathways of communication between the neuronal–glial–epithelial unit and the brain. The neural pathway, immune pathway and endocrine pathway are three main pathways that exist between the gut and brain, which microbiota can modulate the gut–brain axis.

Figure 4

The neuronal–glial–endothelial unit is an entity which combines both anatomy and function. The epithelial cells are on the front line and ENS interspersed in the following muscular and connective tissue. Scattered immune cells, APCs, and neurons communicate with each other in favor of the complex cellular network. Various cytokines and signal molecules such as LPS, 5-HT, and SCFA target to regulate the neuronal–glial–endothelial unit activity.