Claudins and barrier dysfunction in intestinal inflammation: cause or consequence?

The intestinal epithelium forms a barrier between the body and the external environment facilitating the selective uptake of water, ions and nutrients while excluding bacteria, antigens and toxins. This raises the question whether breaches in this barrier can be a primary cause of intestinal inflammation or whether barrier loss is merely the inevitable consequence of inflammation causing epithelial damage, without barrier loss itself playing a pathogenic role. This question has puzzled investigators for decades and is of some importance, as the answer will determine whether restoring barrier loss is a plausible target for future therapy. Doubts about barrier loss playing an important causal role in inflammation have been fuelled by observations that some healthy individuals have an impaired barrier as measured by sugar absorption studies and in some circumstances barrier loss may actually be protective against intestinal inflammation.1 ,2 The intestinal barrier comprises a physical barrier provided by epithelial cells and the overlying mucus and a chemical barrier of antibacterial peptides secreted by Paneth cells. The main physical barriers are the epithelial cells and the intercellular spaces between them. The absorption of substances between epithelial cells is termed paracellular transport. The rate-limiting structure for paracellular transport is the tight junction; a complex branching network of proteins bringing the cell membranes of neighbouring cells almost together near the luminal surface of the epithelial …