Mucins in Intestinal Mucosal Defense and Inflammation: Learning From Clinical and Experimental Studies

Abstract

Throughout the gastrointestinal (GI) tract, a distinct mucus layer composed of highly glycosylated proteins called mucins plays an essential role in providing lubrication for the passage of food, participating in cell signaling pathways and protecting the host epithelium from commensal microorganisms and invading pathogens, as well as toxins and other environmental irritants. These mucins can be broadly classified into either secreted gel-forming mucins, those that provide the structural backbone for the mucus barrier, or transmembrane mucins, those that form the glycocalyx layer covering the underlying epithelial cells. Goblet cells dispersed among the intestinal epithelial cells are chiefly responsible for the synthesis and secretion of mucins within the gut and are heavily influenced by interactions with the immune system. Evidence from both clinical and animal studies have indicated that several GI conditions, including inflammatory bowel disease (IBD), colorectal cancer, and numerous enteric infections are accompanied by considerable changes in mucin quality and quantity. These changes include, but are not limited to, impaired goblet cell function, synthesis dysregulation, and altered post-translational modifications. The current review aims to highlight the structural and functional features as well as the production and immunological regulation of mucins and the impact these key elements have within the context of barrier function and host defense in intestinal inflammation.

DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice

“…Given the fact that endotoxemia is one of the common features of IBD and metabolic disorders, we hypothesized that an impaired intestinal barrier function caused by DSS treatment triggers LPS-induced systemic inflammation that could lead to disturbed energy homeostasis. Several studies have shown that in the pathogenesis of DSS-induced colitis, the intestinal epithelial barrier dysfunction is associated with the disruption of tight junction proteins 45 , 46 , as well as mucus layer proteins 47 . Mice with DSS-induced colitis used in this study consistently showed decreased expression of ZO-1, occludin, MUC2, and MUC13 (Figs.…”

Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications

“…Importantly, similar changes have been described in patients suffering from NEC [16][17][18]22], which suggests that a loss of goblet cells in utero may predispose to NEC development. Reduced goblet cell numbers are associated with a disturbed mucus layer [39] and, thus, a reduced intestinal barrier function, which makes a neonate upon birth more vulnerable during the crucial period of microbial colonization. In addition, the increase of CHOP-positive cells in the crypt at 8-15 d after IA LPS exposure implies that the intestine is prone to a second wave of apoptosis, either following ongoing (intrauterine) inflammation or after additional postnatal inflammatory hits such as mechanical ventilation [40] or sepsis [41].…”

Gut Microbiota Comparison Between Intestinal Contents and Mucosa in Mice With Repeated Stress-Related Diarrhea Provides Novel Insight

“…So, intestinal epithelial disorder may occur in diarrhea mice in this study. Intestinal epithelial disorder is one of the pathological features of functional bowel disease including stress-related diarrhea ( Grondin et al, 2020 ; Kim et al, 2020 ). The overall trend of microbiota community structure is an increase in pathogenic bacteria and a decrease in beneficial bacteria in both intestinal mucosa and intestinal contents.…”

“…Moreover, we predicted the function of bacterial genes and found that there were disorders of amino acid metabolism, including the amino acid nitrogen fixation pathway, caused by microbiota in the intestinal mucosa. The results showed that bacterial genes mainly induced intestinal inflammation through the FoxO signaling pathway ( Douglas et al, 2015 ) and MAPK signaling pathway ( Grondin et al, 2020 ) and participated in neural response. It is suggested that the metabolic activities of intestinal microbiota are involved in the brain–gut nerve response, including tryptophan metabolism.…”