Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier.

Giovanni Barbara,Giovanni Marasco,Vincenzo Stanghellini,Marta Palombo,Maria Raffaella Barbaro,Cesare Cremon,Daniele Fuschi,Francesca Falangone

doi:10.3389/fnut.2021.718356

Giovanni Barbara, Giovanni Marasco + Show 6 more

Open Access

https://doi.org/10.3389/fnut.2021.718356

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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.

Highlights

The gastrointestinal (GI) tract, with a surface area of about 40 m2, is one of the largest interfaces between the environment and the internal milieu of the body [1, 2]
We have recently demonstrated that Lactobacillus paracasei CNCM I-1572 modulates gut microbiota structure and function and reduces intestinal immune activation in patients with irritable bowel syndrome (IBS)
We have recently reported that zonulin serum levels are significantly increased in non-celiac gluten sensitivity (NCGS) compared to IBS

Summary

INTRODUCTION

The gastrointestinal (GI) tract, with a surface area of about 40 m2, is one of the largest interfaces between the environment and the internal milieu of the body [1, 2]. The mucus layer covers the luminal surface of the GI tract and is the first line of defense against mechanical, chemical, and biological insults It protects epithelial cells from bacteria, digestive enzymes, and dangerous substances coming from the outside including environmental pollutants, food antigens, toxins [9, 10]. Over acting as a physical barrier, it is essential in the maintenance of intestinal homeostasis as small molecules, gases, ions, and water diffuse through it to reach the epithelium [11, 12] It is continuously secreted in the GI tract principally by goblet cells, and from epithelial cells and glands [12]. 31.6 Endothelial tissue: endothelial cells [93] Barrier forming and brain capillary [94]

24.8 Epithelial tissue

Findings

CONCLUSIONS