The esophageal mucosal barrier in health and disease: mucosal pathophysiology and protective mechanisms

Abstract

Diseases of the esophagus, such as gastroesophageal reflux (GER), can result in changes to mucosal integrity, neurological function, and the microbiome. Although poorly understood, both age and GER can lead to changes to the enteric nervous system. In addition, the esophagus has a distinct microbiome that can be altered in GER. Mucosal integrity is also at risk due to persistent damage from acid. Diagnostic tools, such as ambulatory pH/impedance testing and esophageal mucosal impedance, can assess short-term and longitudinal GER burden, which can also assess the risk for mucosal compromise. The quality of the mucosal barrier is determined by its intercellular spaces, tight junctions, and tight junction proteins, which are represented by claudins, occludins, and adhesion molecules. Fortunately, there are protective factors for mucosal integrity that are secreted by the esophageal submucosal mucous glands and within saliva that are augmented by mastication. These protective factors have potential as therapeutic targets for GER. In this article, we aim to review diagnostic tools used to predict mucosal integrity, aging, and microbiome changes to the esophagus and esophageal mucosal defense mechanisms.

Quercetin Improves Mitochondrial Function and Inflammation in H2O2-Induced Oxidative Stress Damage in the Gastric Mucosal Epithelial Cell by Regulating the PI3K/AKT Signaling Pathway

“…Our current study indicated that compared to Model group, Que decreased the proportion of cells with an increase in ROS generation and decrease in MMP, alleviated the swollen malformation of ridges in mitochondria, and increased the phosphorylation of DRP1 and the expression of MFN2 and Bcl-2, and decreased the expression of Bax and cleaved caspase 3, indicating the improvement effect of Que on mitochondrial dysfunction induced by oxidative stress response. In addition, this work reported that Que repairs the cellular barrier by regulating tight junction proteins occludin, claudin-1, and ZO-1 [ 48 , 49 ].…”

Laryngeal and Esophageal Mucosal Protection Using the Angico Gum Biopolymer in a Mouse Model of Reflux

“…14 The relationship between inflammatory processes and loss of mucosal integrity is apparently well correlated. 3,30,31 However, it is questionable, considering that treatment with hyaluronic acid improved inflammatory aspects, but had no effect in preventing mucosal integrity. 14 Considering that inflammatory response is a complex event associated with multiple mediators and cellular mechanisms, we cannot rule out the possibility that there are other inflammatory mechanisms involved in the reduction of laryngeal barrier function.…”

“…In this context, studies have demonstrated that cashew gum is also able to prevent the loss of mucosa in the larynx 14 . The relationship between inflammatory processes and loss of mucosal integrity is apparently well correlated 3,30,31 . However, it is questionable, considering that treatment with hyaluronic acid improved inflammatory aspects, but had no effect in preventing mucosal integrity 14 .…”

“…Laryngopharyngeal reflux (LPR) is one such extraesophageal disorder in which the gastric content flows to the laryngopharyngeal region, causing symptoms of hoarseness and dysphagia. 3,4 The gold standard treatment for LPR is the use of proton pump inhibitors (PPIs); however, remission after therapy is approximately 50%. 5 Some factors related to this therapeutic failure are an incorrect diagnosis of LPR, difficulty in dose standardization, long treatment duration, 6,7 and the ineffectiveness of PPIs in the treatment of nonacid reflux.…”

“…Gastric contents refluxed from the stomach to adjacent organs cause esophageal and extraesophageal disorders. Laryngopharyngeal reflux (LPR) is one such extraesophageal disorder in which the gastric content flows to the laryngopharyngeal region, causing symptoms of hoarseness and dysphagia 3,4 . The gold standard treatment for LPR is the use of proton pump inhibitors (PPIs); however, remission after therapy is approximately 50% 5 …”