Roles and regulation of the mucus barrier in the gut

Abstract

The gastrointestinal tract is coated by a thick layer of mucus that forms the front line of innate host defense. Mucus consists of high molecular weight glycoproteins called mucins that are synthesized and secreted by goblet cells and functions primarily to lubricate the epithelium and protect it from damage by noxious substances. Recent studies have also suggested the involvement of goblet cells and mucins in complex immune functions such as antigen presentation and tolerance. Under normal physiological conditions, goblet cells continually produce mucins to replenish and maintain the mucus barrier; however, goblet cell function can be disrupted by various factors that can affect the integrity of the mucus barrier. Some of these factors such as microbes, microbial toxins and cytokines can stimulate or inhibit mucin production and secretion, alter the chemical composition of mucins or degrade the mucus layer. This can lead to a compromised mucus barrier and subsequently to various pathological conditions like chronic inflammatory diseases. Insight into how these factors modulate the mucus barrier in the gut is necessary in order to develop strategies to combat these disorders.

Keywords:

• Innate defense
• Barrier function
• Secretory response
• Goblet cell
• MUC2
• Mucin
• ER stress
• Unfolded protein response
• IBD

Abbreviations:

• GI, gastrointestinal
• SCFA, short chain fatty acids
• GalNAc, N-Acetylgalactosamine
• MucBP, Mucin binding proteins
• LLO, Listeriolysin O
• EhCP5, Entamoeba histolytica cysteine protease 5
• LPS, Lipopolysaccharide
• IBD, Inflammatory bowel disease
• UC, Ulcerative colitis
• CD, Crohns disease
• UPR, unfolded protein response
• ERAD, ER-associated protein degradation
• FAS, fatty acid synthase

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

Research presented in this review was support by grants from the Canadian Institute for Health Research (CIHR) and Crohn's and Colitis Canada. SC is supported by an NSERC CREATE HPI scholarship and AT by the Eleanor Mackie doctoral scholarship in women's health. KC holds a Tier 1 Canada Research Chair supported by CIHR.