Mucin Structure and Types
Glycans covalently attach to the polypeptide chains through the amide
nitrogen of asparagine side-chain (N-linked), the hydroxyl group of
serine/threonine side-chains (O-linked), or the thiol group of cysteine
side-chain (S-linked)15. Epithelial glycans are major
components of the intestinal mucus and regulators of the interaction
between the gut microbiota and the gut epithelia134.
The mucus is composed of proteins, salts, lipids, immunological factors,
and a hydrogel layer made up of mucins (MUCs) 135.
Mucins are glycoproteins produced by goblet cells and can be broadly
classified as secreted or membrane mucins136. They are
heavily O-glycosylated (nearly 80%) by the host Golgi apparatus and
contain large peptide domains with repeating proline, threonine, and
serine amino acids (the PTS domain) (Fig. 3)137175.
Mucin glycosylation and the number of repeats depend on the cell
lineage, developmental stage, and anatomical
section137-139. These O-linked oligosaccharides are
mainly composed of N-acetyl galactosamine (GalNAc), N-acetyl glucosamine
(GlcNAc), galactose (Gal), sialic acid (Sia), and fucose
(Fuc)137,140,141. The number of O-linked
oligosaccharides in mucin is proportional to its molecular weight.
Increased glycosylation also leads to increased water absorption and
relative expansion of the mucus layer, which leads to a greater
barrier141. In addition, O-glycosylation of mucins
helps protect the mucus layer from bacterial
proteases142.
Transmembrane mucins, for instance, MUC1, MUC3, and MUC4 are major
components of the glycocalyx143. Secreted mucins form
the mucus layer. Mucin 2 (MUC2) glycoprotein mostly forms the secreted
mucus layer in the colon and small intestine, while MUC5 and MUC6 can be
found in the secreted mucus layer in the stomach144.
The colonic mucus has two layers (a denser inner layer that is largely
free of bacteria and a looser outer layer that contains some bacteria);
the small intestine has a mucus structure composed of only one layer
(Fig. 1)145. The interplay between the gut mucins and
the gut microbiota is important to establish a healthy mucus layer as
mucin glycosylation shapes the nature and diversity of mucus and is a
major contributor to the gut microbiota diversity and
function146. The mucus layer is a habitat for bacteria
since it contains attachment sites for the
bacteria147,148. The impaired mucus layer grants
access to the bacteria to reach the epithelial layer and cause
inflammation (Fig. 2A)149.