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The intestinal mucus prevents the penetration of microbes and also serves as a nutrient source. It is utilized by many bacterial species including Bifidobacterium, Bacteroides, and Akkermansia muciniphila.
Commensal colonic bacteria colonize the outer mucus layer and also the surface of the inner mucus layer. This is the primary site of interaction between bacteria and the host. Some commensal bacteria can utilize mucin O-glycans. But bacterial degradation and mucin turnover are tightly controlled. This provides an ideal environment for microbiota. They thrive while accessing a range of dietary and host glycans.
We describe the generation and characterization of the human colon or ileum organoid models capable of functional differentiation into mature epithelial cell types. In monolayer culture, these cells formed a robust epithelial barrier with sustained transepithelial electrical resistance (TEER). This was damaged by the inflammatory cytokines IFN-gamma and TNF-alfa
The second layer of the intestinal barrier is the mucin, consisting of heavily glycosylated proteins secreted by the intestinal goblet cells
The mucus barrier covers the intestinal epithelium in the small intestine in one layer, and in the large intestine in two layers. The mucus is produced by goblet cells in specialized intestinal wall epithelial cells.
The colon Mucus layer consists of secreted mucin proteins containing O-linked glycans.
It is an epithelial barrier, consisting of the enterocytes with the tight junction proteins, the Paneth cells, secreting antimicrobial peptides, and the goblet cells, secreting mucin
The gastrointestinal epithelial layer forms invaginations. These are called glands in the stomach and crypts of Lieberkühn in the intestine. In the small intestine, villi extend into the lumen. This maximizes nutrient uptake. It also helps counteract infections. The body invests in cell turnover at the surface of these invaginations. Adult stem cells are found here. They constantly proliferate. They produce undifferentiated progenitor cells. These are transit-amplifying cells in the intestine and Isthmus cells in the stomach. Cells below this amplification region live longer. Small intestinal Paneth cells live 3–6 weeks. Gastric glandular cells, like chief cells, live several months. Cells above the amplification region move towards the surface. They reach the gastric pit, small intestinal villus, or colon crypt opening. They are shed into the lumen after about 3–5 days. Both organs have absorptive enterocytes and secretory cells. These include mucus-producing goblet cells, hormone-producing enteroendocrine cells, and tuft cells. The small intestine also has Paneth cells. They produce antibacterial peptides. It also has specialized microfold (M) cells on Peyer’s patches. These enable crosstalk between the microbiota and the immune system.
The Lamina propria containing different immune cells of innate and adaptive immunity
The outer layer comprises the mucus layer, the Commensal Bacteria / Commensalism, and defense proteins such as antimicrobial proteins (AMPs) and secretory immunoglobulin A (sIgA)
The glycoprotein MUC2 constitutes most of the colonic mucus layer
Akkermansia, Bacteroides, Bifidobacterium, and Ruminococcus closely interact with the intestinal mucus layer and are, therefore, mucosal bacteria. Cell wall or membrane proteins, polysaccharides, and extracellular vesicles facilitate these mucosal bacteria-host interactions. The mucus layers protect the epithelia and the respiratory and urinary tract against pathogens and mechanical damage (barrier integrity).
If the mucosal barrier is damaged by dysbiosis , PAMPs (pathogen-associated molecular patterns) such as Lipopolysaccharides (LPS) enter the tissue (= endotoxemia) and stimulate inflammation
The role of the mucus layer is to protect intestinal cells from external agents and facilitate nutrient absorption
The semipermeable gut barrier is a large contact area with the external environment to selectively absorb nutrients and electrolytes, and resist the invasion of antigen and gut microbes
The intestinal barrier prevents translocation of intestinal microbes into internal compartments. The barrier epithelium plays a fundamental role in the immune defense against enteric viral infections. It integrates various signals, including those from the microbiota, to prevent diseases.
For example, several studies indicated that the outer mucus layer is enriched in Mucin Degrading Bacteria, such as Akkermansia muciniphila (in mice and humans: ; ), Bacteroides fragilis (in mice: ; ), Bacteroides thetaiotaomicron (in mice: ), Bacteroides vulgatus / Phocaeicola vulgatus (in humans: ), Ruminococcus gnavus (in humans: ), Ruminococcus torques (in humans: ), and Bifidobacterium bifidum (in humans: ; )
The mucosa prevents microbes from directly interacting with epithelial cells
Five distinct types of cells compose the epithelium of the intestinal barrier are enterocytes (absorbing water and electrolytes), goblet cells (secreting mucus), enteroendocrine cells (secreting hormones), Paneth cells (secreting anti-microbial peptides), and microfold or “membranous” cells. In addition, these cells are renewed by a pool of stem cells residing in the intestinal crypts
The intestinal mucus is built around MUC2 mucin. It is highly glycosylated. Some commensal bacteria specialize in binding and degrading glycans on mucins. These glycans ikely play a key role in microbial colonization.
The gel-like outer mucus layer is associated with a unique microbial community compared with the lumen microbiome
Our findings reveal a fundamental mechanism by which the immune system is able to support intestinal epithelium, activating intestinal stem cells to promote regeneration
In the small intestine, bacteria due to peristalsis stay briefly. Although the mucus is penetrable but bacteria are kept away from epithelial cells, because continuous mucus secretion and antibacterial peptides achieve this.
At least three additional cell types exist in the intestinal epithelium: microfold or ‘‘membranous’’ (M) cells, cup cells, and tuft cells
The human mucus layer is also persistently colonized by hydrogenotrophic microbes , including sulfate-reducing bacteria (SRB), such as Desulfovibrio piger, Desulfovibrio desulfuricans , and Bilophila wadsworthia
The gut barrier is composed of multiple barriers. Each barrier interacts with each other to maintain the semi-permeable stability
The level of maturity of the neonatal gut varies between species, depending on the length of the gestation period
Hematopoietic cells, such as mononuclear cells and innate lymphoid cells (ILCs), are important effector cells of the innate immune system
The mucosa is also a nutrient source for many strains within the families Clostridiaceae, Akkermansiaceae, Bifidobacteriaceae, and Bacteroidaceae, all of which have been shown to change with age
Colonic bacteria are separated from epithelial cells by an inner mucus layer.
Mucin glycoproteins are secreted from goblet cells form two distinct mucus structures in the mammalian colon: a gel-like outer mucus layer and an inner mucus layer
The outer layer can be washed off easily and Is colonized by bacteria
Several cytokines are known to increase permeability in the intestinal epithelial monolayer (eg, TNF-alfa , IFN-gamma, Interleukin-4 (IL-4) and IL-13 ), by modulating tight junction protein expression and localisation. The observed inhibition of cytokine expression by Activation / Activators & Farnesoid X Receptor (FXR / NR1H4) may therefore represent a possible mechanism for the preservation of intestinal permeability
Adams et al. 1993 J Immunol 150: 2356-63
see also:
Akkermansia muciniphila & Mucosa / Mucous membrane
Defense Systems / Defense Mechanisms
Glycan-degrading carbohydrate-active enzymes (CAZymes) / CAZy
Intestine / Gastrointestinal Tract (Gut / GIT)
Mucin Degrading Bacteria
Mucins & O-Glycans / O-Linked Glycosylation
Mucosa / Mucous membrane