What is the leaky gut? Clinical considerations in humans

Abstract

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.

The Impact of Zinc and Zinc Homeostasis on the Intestinal Mucosal Barrier and Intestinal Diseases

“…An in vitro study by Miyoshi et al [ 38 ] also found that the tight junction permeability in Caco2 cells increased in the presence of zinc deficiency, and cell viability was significantly reduced. Furthermore, the repair and regeneration of the intestinal mucosa requires the participation of zinc; so, exogenous supplementation can maintain the integrity of the intestinal mucosal barrier morphology and function [ 39 ]. These results suggest that zinc plays an important role in maintaining the intestinal barrier function.…”

Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy

“…These are also the studies (models) most fraught with issues of inherent variability emanating from individual differences in genetics, age, diet and medications—perhaps not a coincidence, then, that they are in scarcity. Camilleri [ 383 ] very validly points out in a recent review that it has never been conclusively proven that although micronutrient fortification of (intestinal) epithelial barrier leakiness is apparently quite real, conclusive evidence showing true amelioration of disease-related clinical manifestations by barrier-enhancing micronutrients has been elusive.…”

Cross-Talk between Probiotic Nissle 1917 and Human Colonic Epithelium Affects the Metabolite Composition and Demonstrates Host Antibacterial Effect

“…Our metabolome data indicate that several metabolites are differently distributed between apical and basolateral compartments (e.g., Asp, succinic acid). This might be due to tight junctions (TJs) that create a tightly regulated diffusion barrier between colonic luminal and serosal content for ions, small and large molecules [54,55]. Dysfunctional TJ contributes to multiple diseases, such as ulcerative colitis [55].…”

“…This might be due to tight junctions (TJs) that create a tightly regulated diffusion barrier between colonic luminal and serosal content for ions, small and large molecules [54,55]. Dysfunctional TJ contributes to multiple diseases, such as ulcerative colitis [55]. It is well known that pathogenic bacteria and some commensals might contribute to the loss of TJ integrity leading to transepithelial movements of bacterial toxins, such as lipopolysaccharides.…”