The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls

The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different regulatory mechanisms jointly collaborate to maintain intestinal homeostasis, but alterations in these mechanisms lead to a dysfunctional gastrointestinal barrier and are associated to several inflammatory conditions usually found in chronic pathologies such as inflammatory bowel disease (IBD). The gastrointestinal mucus, mostly composed of mucin glycoproteins, covers the epithelium and plays an essential role in digestive and barrier functions. However, its regulation is very dynamic and is still poorly understood. This review presents some aspects concerning the role of mucus in gut health and its alterations in IBD. In addition, the impact of gut microbiota and dietary compounds as environmental factors modulating the mucus layer is addressed. To date, studies have evidenced the impact of the three-way interplay between the microbiome, diet and the mucus layer on the gut barrier, host immune system and IBD. This review emphasizes the need to address current limitations on this topic, especially regarding the design of robust human trials and highlights the potential interest of improving our understanding of the regulation of the intestinal mucus barrier in IBD.

Download Full-text

The Impact of MicroRNAs during Inflammatory Bowel Disease: Effects on the Mucus Layer and Intercellular Junctions for Gut Permeability

Cells ◽

10.3390/cells10123358 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3358

Author(s):

Sarah Stiegeler ◽

Kevin Mercurio ◽

Miruna Alexandra Iancu ◽

Sinéad C. Corr

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

The Body ◽

Proper Function ◽

Epithelial Barrier ◽

Mucus Layer ◽

Gut Permeability ◽

Epithelial Junctions ◽

Inflammatory Bowel ◽

The Impact

Research on inflammatory bowel disease (IBD) has produced mounting evidence for the modulation of microRNAs (miRNAs) during pathogenesis. MiRNAs are small, non-coding RNAs that interfere with the translation of mRNAs. Their high stability in free circulation at various regions of the body allows researchers to utilise miRNAs as biomarkers and as a focus for potential treatments of IBD. Yet, their distinct regulatory roles at the gut epithelial barrier remain elusive due to the fact that there are several external and cellular factors contributing to gut permeability. This review focuses on how miRNAs may compromise two components of the gut epithelium that together form the initial physical barrier: the mucus layer and the intercellular epithelial junctions. Here, we summarise the impact of miRNAs on goblet cell secretion and mucin structure, along with the proper function of various junctional proteins involved in paracellular transport, cell adhesion and communication. Knowledge of how this elaborate network of cells at the gut epithelial barrier becomes compromised as a result of dysregulated miRNA expression, thereby contributing to the development of IBD, will support the generation of miRNA-associated biomarker panels and therapeutic strategies that detect and ameliorate gut permeability.

Download Full-text

Mucosal bacterial microﬂora and mucus layer thickness inadolescents with inﬂammatory bowel disease

World Journal of Gastroenterology ◽

10.3748/wjg.15.5287 ◽

2009 ◽

Vol 15 (42) ◽

pp. 5287 ◽

Cited By ~ 81

Author(s):

Krzysztof Fyderek ◽

Magdalena Strus ◽

Kinga Kowalska-Duplaga ◽

Tomasz Gosiewski ◽

Andrzej Wędrychowicz ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Layer Thickness ◽

Bowel Disease ◽

Mucus Layer ◽

Inflammatory Bowel

Download Full-text

Catestatin regulates the colonic mucus layer in inflammatory bowel disease

10.1101/2021.02.09.430377 ◽

2021 ◽

Author(s):

Elke M. Muntjewerff ◽

Lisanne Lutter ◽

Kechun Tang ◽

Mariska Kea-te Lindert ◽

Jack Fransen ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bone Marrow ◽

Bowel Disease ◽

Immune Cell ◽

Mucus Layer ◽

Coding Region ◽

Colon Tissue ◽

Exact Role ◽

Mucus Production ◽

Inflammatory Bowel

AbstractBackgroundThe pro-hormone chromogranin A (CgA) and its bioactive cleavage product catestatin (CST) are both associated with inflammatory bowel disease (IBD) and dysregulated barrier functions, but their exact role has remained elusive. Here, we demonstrate that CST regulates the colonic mucus layer.MethodsCST levels were measured in feces of IBD patients. The mucus layer, goblet cells, and immune cell infiltration were analyzed by histology and electron microscopy in colon tissue from IBD patients and mice with selective deletion of the CST-coding region of the CgA gene.ResultsCST levels were elevated in feces of IBD patients compared to healthy controls. The thickness of the mucus layer was increased in non-affected, but not in inflamed, regions of the colon in IBD patients. The thickness of the mucus layer and concomitant mucus production were also increased in the CST-KO mouse. This mucus phenotype in CST-KO mice could be reversed by bone marrow transplantation from wildtype mice.ConclusionsCST produced by bone-marrow derived immune cells reduces production of the mucus layer in the intestine. This might contribute to the reduced mucus layer in inflamed colon regions of IBD patients. Additionally, CST feces levels might be a biomarker for IBD.

Download Full-text

Mucins Dynamics in Physiological and Pathological Conditions

International Journal of Molecular Sciences ◽

10.3390/ijms222413642 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13642

Author(s):

Hassan Melhem ◽

Daniel Regan-Komito ◽

Jan Hendrik Niess

Keyword(s):

Inflammatory Bowel Disease ◽

Epithelial Cells ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Goblet Cells ◽

Mucus Layer ◽

Intestinal Mucus ◽

Pathological Conditions ◽

Inflammatory Bowel ◽

Mucus Barrier

Maintaining intestinal health requires clear segregation between epithelial cells and luminal microbes. The intestinal mucus layer, produced by goblet cells (GCs), is a key element in maintaining the functional protection of the epithelium. The importance of the gut mucus barrier is highlighted in mice lacking Muc2, the major form of secreted mucins. These mice show closer bacterial residence to epithelial cells, develop spontaneous colitis and became moribund when infected with the attaching and effacing pathogen, Citrobacter rodentium. Furthermore, numerous observations have associated GCs and mucus layer dysfunction to the pathogenesis of inflammatory bowel disease (IBD). However, the molecular mechanisms that regulate the physiology of GCs and the mucus layer remain obscured. In this review, we consider novel findings describing divergent functionality and expression profiles of GCs subtypes within intestinal crypts. We also discuss internal (host) and external (diets and bacteria) factors that modulate different aspects of the mucus layer as well as the contribution of an altered mucus barrier to the onset of IBD.

Download Full-text