Intestinal permeability: functional assessment and significance.

The intestinal epithelium demonstrates differential properties, providing both barrier and transport functions with respect to luminal molecules. Intestinal permeability relates to barrier function and, although it is the ‘permeation’ of molecular markers that is used to measure ‘permeability’, the terms are often confused. Permeability is that property of the intestinal epithelium or of a membrane which refers to the facility with which it allows molecules to pass through by non-mediated diffusion [ 11, whereas the term permeation describes the act of nonmediated diffusion itself. Non-mediated diffusion means the passage of molecules down a concentration (or pressure) gradient without the assistance of a passive or active biochemical carrier system. Intestinal permeability in a clinical context mainly concerns the permeation of molecules with a molecular mass > 150 Da, rather than ions such as sodium or chloride, to which the term membrane permeability is usually applied. In some respects the barrier function shows dynamic properties [2], as shown by the observation that altered permeability induced by hyperosmotic stress is reversible within a few hours [3]. Intestinal barrier function is also affected by disease, drugs, diet, cytokines, hormones or the environment, but does not appear to be much influenced by age, race or hereditary factors. The consequences of impaired barrier function for antigen access [4], which could initiate or perpetuate inflammation, and the potential for non-invasive assessment of disease or therapeutic manipulation, are reasons for the current interest in intestinal permeability. This review is divided into two parts. The first part outlines the nature of the intestinal epithelial barrier and our still incomplete understanding of the pathways of permeation, as well as mechanisms by which permeability can be altered. The second part discusses methods available for measuring intestinal permeability in vivo, the clinical circumstances in which it is altered, and the relevance of clinical tests of permeability. First, a brief history of intestinal permeability is appropriate.