What is the leaky gut? Clinical considerations in humans

PURPOSE OF REVIEW: To review the components of the intestinal barrier, the practical measurements of intestinal permeability, and the clinical conditions associated with altered intestinal barrier function, and to summarize the effects of dietary substances that fortify or weaken the intestinal barrier. RECENT FINDINGS: The intestinal barrier includes surface mucus, epithelial layer, and immune defense mechanisms. Transport across the epithelium may result from increased paracellular transport, apoptosis, or transcellular permeability. Assessment of the intestinal barrier requires measurements beyond the transport across the epithelial layer or the measurement of tight junction expression. Barrier function is most meaningfully tested in vivo using orally administered probe molecules; other approaches are performed in vitro using mucosal biopsies from humans, or exposing colonic mucosa from rats or mice or cell layers to extracts of colonic mucosa or stool from patients. Dietary factors can influence intestinal leakiness: fortifying the barrier with vitamins A and D, zinc, short-chain fatty acids, methionine, glutamine, and probiotics; weakening of the barrier has been reported with fat, bile acids, emulsifiers, and gliadin. Intestinal mucosal leakiness in 'stress' disorders such as major burns is reversed with enteral glutamine. SUMMARY: Inflammatory or ulcerating intestinal diseases result in leakiness of the gut barrier; however, no such disease has been cured by simply normalizing intestinal barrier function. Similarly, it is still unproven that restoring barrier function (reversing 'leaky gut') can ameliorate clinical manifestations in nonulcerating gastrointestinal disease or systemic or neurological diseases. On the other hand, dietary and enteral interventions can fortify the intestinal barrier in stress-associated states.