Mucus

The gastrointestinal tract contains tremendous numbers of microorganisms and some of these microorganisms are pathogenic in nature under certain conditions. Therefore a function of the mucus is to protect the underlying epithelial cells by keeping the microbes and toxins at bay, on the outer mucosal surfaces. The mucus layer is comprised of various mucosal secretions including mucins, trefoil peptides, and surfactant phospholipids.

Mucus occurs in two distinct physical forms: (1) a thin layer of stable, water insoluble mucus gel firmly adhering to the gastroduodenal mucosal surface, (2) and as soluble mucus which is quite viscous but mixes with the luminal juice (7).

The layer of mucus that is bound to the surface of the gastrointestinal tract is resistant to its removal from the mucosa. It is approximately 50-450 mm thick in humans and about twofold less in rats. This adherent mucus functions to support and define the mucosal ecosystem since it is the outermost sensory "organ" of the mucosal immune system. The mucus gel plays a role in providing surface neutralization by having the HCOK barrier to the gastric acid. The surfactant lipids maintain surface hydrophobicity on the mucus. The adherent mucus also serves as a stable protective barrier that prevents the entry of luminal pepsin to the underlying epithelial cells.

The soluble mucus plays a role in maintaining the protective barrier because it is not physically attached to the mucosa and can be removed from the mucosa by gentle washing. Due to the viscous nature of the soluble mucus, the soluble mucus makes an excellent lubricant which allows easy movement of solid material in the lumen. This helps to prevent the damage to the underlying epithelial cells as well as minimize the tearing of the adherent layer of mucus from the mucosal surface (7).

The main structural component of the mucus layer are the mucins or glycoproteins of molecular weight ranging from one to several million daltons. When concentrated, these glycoprotein macromolecules (Mr>2X106) polymerise to form gels. Mucin molecules consist of carbohydrate side chains (70-80%) bound to a protein skeleton. The O-linked oligosaccharide chains contain a restricted number of monosaccharides, including galactose, fucose, N-acetylgalactosamine, N-acetylglucosamine and often terminated with sialic acids or sulfate groups, which account for the polyanionic nature of mucins at a neutral pH (7,8). Oligosaccharides chains are successively added on to mucins specifically by membrane bound glycosyltransferases. The biochemistry of the intestinal mucins confers their protective nature: the protein backbone has a high O-linked oligosaccharide content (>80% carbohydrate by mass) that provides lectin-binding capacity, whereas the ability of the protein core to form multimers (through disulphide bonds) causes polymerization into gels and bestows viscoelasticity and lubrication (9). The trefoil peptides also facilitate the mucins to confer visoelasticity on the mucus (10).

The composition of the mucus is constantly regulated by the varying secretion rates of the mucin types, ions, lipids, proteins and water. The variation in the composition of the mucus is also dependent on the development stage of the host as well as the host's diet and the interaction of the commensals and pathogens (10). Commensals rapidly colonize the individual soon after birth and some play a role in inhibiting the growth of pathogenic bacteria. However, many commensals are capable of becoming opportunistic pathogens by overgrowing when the stable gastrointestinal ecosystem is disturbed. Thus, the mucus has to be continuously secreted and then shed, discarded, digested or recycled. This form of protective mechanism keeps the numbers of both pathogens and commensals in check by blocking the bacterial adherence to the epithelial cells.

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