Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier

Abstract

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.

Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis

“…Although the severe outcomes of induced colitis were marked, the more subtle impact that loss of Zbtb20 in T cells had on the maintenance of the intestinal epithelial barrier (IEB) integrity may ultimately be of greater importance. The IEB has multiple functions including preventing the release of potentially harmful pathogens and antigens while also directly aiding in the absorption of nutrients and water (53). Hence, IEB integrity is associated with a broad range of diseases including inflammatory bowel disease (IBD), irritable bowel syndrome, and even Celiac disease (54)(55)(56).…”

Probiotics, Their Extracellular Vesicles and Infectious Diseases

“…The intestinal epithelial barrier acts as the first line of defense by avoiding the entrance of antigens and pathogens ( Barbara et al, 2021 ). The alteration of the gut microbiota is the most important factor that disrupts the integrity of the intestinal epithelial barrier, leading to intestinal inflammation and diseases ( Gareau et al, 2010 ).…”

“…As for the physical barrier, in vitro and in vivo experiments have demonstrated that EVs released by E. coli Nissle 1917 can mediate anti-inflammatory effects and protect the intestinal epithelial barrier function ( Alvarez et al, 2016 ; Fábrega et al, 2016 , 2017 ). A key role in the maintenance of intestinal epithelial barrier integrity is played by tight junctions, which are composed of a network of proteins that regulate paracellular permeability, such as claudins, zonula occludens (ZO) and occludin ( Barbara et al, 2021 ). EVs released by E. coli Nissle 1917 have been shown to upregulate ZO-1 and claudin-14, downregulate claudin-2 (a gene that codes for a leaky protein), and in turn improve epithelial barrier function in an in vitro intestinal epithelium models (T-84 and Caco-2 cell lines) ( Alvarez et al, 2016 ).…”

“…Regarding the intestinal chemical defense, antimicrobial peptides and the mucus layer (mainly produced by the goblet cells) are further key factors that maintain intestinal barrier integrity by protecting epithelial cells from bacteria and other challenges ( Hansson, 2020 ; Yong et al, 2020 ; Barbara et al, 2021 ; Fusco et al, 2021 ). In an in vivo model of experimental colitis, treatment with EVs from E. coli Nissle 1917 resulted in the restoration of the mucin content in goblet cells and in a smaller ulceration surface, as evidence of barrier integrity ( Fábrega et al, 2017 ).…”

Gut microbiota signatures and modulation in irritable bowel syndrome

“…IBS is a multifactorial disorder with a complex and not completely understood pathophysiology [31] . Previously, IBS has been mainly considered a psychosomatic disorder in which psychosocial factors, including stress, anxiety, and depression, markedly contributed to altered motility and visceral hypersensitivity [32] . IBS is now considered a disorder of the gut-brain axis (DGBI) characterized by a complex interplay between peripheral and central factors, including genetic predisposition, alterations in gastrointestinal sensory-motor function, intestinal dysbiosis, increased intestinal permeability, mucosal lowgrade inflammation and immune activation, neuroendocrine abnormalities, food sensitivity, and psychosocial factors [Figure 1] [11,31,33] .…”