Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay

Abstract

Inflammatory bowel disease, irritable bowel syndrome and severe central nervous system injury can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases. Hence, repairing the intestinal barrier represents a potential therapeutic target for many diseases. Enteral afferent nerves, efferent nerves and the intrinsic enteric nervous system (ENS) play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors. In addition, intestinal microorganisms and their metabolites play a regulatory role in the intestinal mucosal barrier. This paper primarily discusses the interactions between norepinephrine and β-adrenergic receptors, cholinergic anti-inflammatory pathways, nociceptive receptors, complex ENS networks, gut microbes and various immune cells with their secreted cytokines to summarize the key roles in regulating intestinal inflammation and improving mucosal barrier function.

The Role of Gastrointestinal Microbiota in Functional Dyspepsia: A Review

“…Studies show that monobutyric acid and monovaleric acid in ScFAs can upregulate the expression of the tight junction protein ZO-1 and thus protect the intestinal mucosal barrier ( Nguyen et al, 2020 ). Intestinal epithelial cells are an important component of the intestinal mucosal barrier and are differentiated from stem cells at the base of the intestinal mucosal crypts, and the maintenance and repair of the intestinal mucosal barrier depends on the normal proliferation and differentiation of these stem cells ( You et al, 2021 ). The Wnt/β-catenin signaling pathway is a key regulator of intestinal epithelial stem cells and plays an important regulatory role in the proliferation and maintenance of intestinal epithelial stem cells ( Koch, 2017 ).…”

Calycosin Improves Intestinal Mucosal Barrier Function after Gastrectomy in Rats through Alleviating Bacterial Translocation, Inflammation, and Oxidative Stress

“…The intestinal mucosal immune barrier is mainly composed of cell populations of gut-associated lymphoid tissue [ 30 ]. Structurally, it is mainly composed of collecting lymphoid nodules, intraepithelial lymphocytes, and lamina propria lymphocytes [ 31 ]. The former is the induction site of mucosal immunity, and the latter two are the effector sites of mucosal immunity [ 32 ].…”

Increased Numbers of Enteric Glial Cells in the Peyer’s Patches and Enhanced Intestinal Permeability by Glial Cell Mediators in Patients with Ileal Crohn’s Disease

“…Moreover, we showed an enhanced bacterial uptake in the FAE of CD patients compared to non-IBD controls [13]. The mechanism underlying the impaired barrier function of Peyer's patches in CD is not fully understood, but neuroimmune interactions involving mast cells and eosinophils have been implicated in the disturbed barrier function [14]. The integrity of the barrier is also known to be regulated by the enteric nervous system (ENS) and the enteric glial cells (EGC) [14,15].…”

“…The mechanism underlying the impaired barrier function of Peyer's patches in CD is not fully understood, but neuroimmune interactions involving mast cells and eosinophils have been implicated in the disturbed barrier function [14]. The integrity of the barrier is also known to be regulated by the enteric nervous system (ENS) and the enteric glial cells (EGC) [14,15]. EGC help to maintain the integrity of the barrier by promoting the proliferation and differentiation of the intestinal epithelial cells, alongside the expression of genes responsible for the maintenance of the barrier.…”