Compromised intestinal barrier function can also cause disease directly, by immunological mechanisms.[6-9] Increased permeability stimulates classic hypersensitivity responses to foods and to components of the normal gut flora; bacterial endotoxins, cell wall polymers and dietary gluten may cause "non-specific" activation of inflammatory pathways mediated by complement and cytokines. [10] In experimental animals, chronic low-grade endotoxemia causes the appearance of auto-immune disorders.[11-13]

Leaky Gut Syndromes are clinical disorders associated with increased intestinal permeability. They include inflammatory and infectious bowel diseases [14-19], chronic inflammatory arthritides [9, 20-24], cryptogenic skin conditions like acne, psoriasis and dermatitis herpetiformis [25-28], many diseases triggered by food allergy or specific food intolerance, including eczema, urticaria, and irritable bowel syndrome [29-37], AIDS [38-40], chronic fatigue syndromes [Rigden, Cheney, Lapp, Galland, unpublished results], chronic hepatitis [41], chronic pancreatitis [4, 5], cystic fibrosis [42] and pancreatic carcinoma. Hyperpermeability may play a primary etiologic role in the evolution of each disease, or may be a secondary consequence of it which causes immune activation, hepatic dysfunction, and pancreatic insufficiency, creating a vicious cycle. Unless specifically investigated, the role of altered intestinal permeability in patients with Leaky Gut Syndromes often goes unrecognized. The availability of safe, non-invasive, and inexpensive methods for measuring small intestinal permeability make it possible for clinicians to look for the presence of altered intestinal permeability in their patients and to objectively assess the efficacy of treatments. Monitoring the intestinal permeability of chronically ill patients with Leaky Gut Syndromes can help improve clinical outcomes.

Triggers and Mediators of the Leaky Gut
Leaky Gut Syndromes are usually provoked by exposure to substances which damage the integrity of the intestinal mucosa, disrupting the desmosomes which bind epithelial cells and increasing passive, para-cellular absorption. The commonest causes of damage are infectious agents (viral, bacterial and protozoan) [43-46], ethanol [47, 48], and non-steroidal anti-inflammatory drugs [20, 49, 50]. Hypoxia of the bowel (occurring as a consequence of open-heart surgery or of shock) [51, 52], elevated levels of reactive oxygen metabolites (biliary, food-borne or produced by inflammatory cells) [53], and cytotoxic drugs [54-56] also increase para-cellular permeability.