Epithelial Barrier Integrity / Mucosal Barrier Integrity

The intestinal epithelium, despite being only a single layer of cells, plays a crucial role in controlling the access of potential antigens and pathogens while simultaneously facilitating the digestive absorption of dietary nutrients. It is aided this dual role by intercellular tight junctions (i.e., adhesive plasma membrane structures) between enterocytes that restrict the passage of even very small (2-kDa) molecules while simultaneously walling the lamina propria from the lumen (7).

Structure

A healthy intestinal epithelium is characterized by an outer and inner Intestinal Epithelial Barrier / Mucosal Barrier / Mucus Layer, which acts as a physical barrier and hosts a diverse gut microbiota. This microbiota supports the functions of mucus and the trophism of epithelial cells (ECs) (1)

The intercellular junctions of the intestinal epithelium, from top to base, include:

1. Tight Junctions (TJs)


2. Adherens Junctions (AJs)


3. Desmosomes

Occludin, important for the formation and disassembly of the Tight Junction proteins, is vital for regulating interactions with Zonula Occludens Protein-1 (ZO-1), essential for maintaining a complete TJ complex and ensuring the paracellular barrier function. Research indicates that short-chain fatty acids (SCFAs) enhance the intestinal barrier by increasing the expression of claudin. Junctional adhesion molecules (JAMs) recruit scaffolding and polarity complex proteins, aiding in establishing basolateral and apical polarity of cell-cell junctions. The engagement of both cadherin and nectin significantly influences the stability of these junctions.

Mucus Barrier and Microbiota

The formation of the protective mucus barrier on the intestinal lumen lining creates a physical space for host-microbe exchange of nutrients and metabolites (2). The response of MUCIN-2 (MUC2) to bacterial toll-like receptor (TLR) ligands can disrupt cytokine transcription, affecting Interleukin-12 (IL-12), Interleukin-6 (IL-6), Chemokine (C-X-C motif) ligand 8 (CXCL8) / Interleukin-8 (IL-8), and Tumor Necrosis Factor alfa (TNF-alfa).

Specialized Cells and Functions

In the small intestine, specialized Microfold cells (M cells) efficiently sample luminal antigens and microbiota. These are then transcytosed through M cells and presented to dendritic cells (DCs) (3)

Factors Affecting Intestinal Health

Secondary fatty acids and toxic metabolites can cause intestinal damage in various ways (4). An intact and functional gut epithelium is essential for maintaining a healthy body (5).

Prostacyclin and PGE2 synergistically restore barrier function in the ileum through intracellular Ca²⁺ and cAMP signaling-dependent mechanisms (6).

References

(1) Petito et al. 2021
(2) Johansson & Hansson 2016 Nat. Rev. Immunol. 16: 639-649
(3) Li et al. 2020s
(4) Meng et al. 2020 J Appl Microbiol 129(4): 787-805
(5) Roy & Trinchieri 2017
(6) Blikslager et al. 1997 J. Clin. Invest. 100: 1928–1933
(7) Madara 1989 J. Clin. Invest. 83:1089–1094

see also:
Adherens Junctions
Intestinal mucosal barrier / Mucus layer & Short-chain fatty acids (SCFAs)
Leaky gut syndrome / Leaky gut