Role of Intestinal Permeability in Monitoring Mucosal Barrier Function

The interaction between host and external environment mainly occurs in the gastrointestinal tract, where the mucosal barrier has a critical role in many physiologic functions ranging from digestion, absorption, and metabolism. This barrier allows the passage and absorption of nutrients, but at the same time, it must regulate the contact between luminal antigens and the immune system, confining undesirable products to the lumen. Diet is an important regulator of the mucosal barrier, and the cross-talk among dietary factors, the immune system, and microbiota is crucial for the modulation of intestinal permeability and for the maintenance of gastrointestinal tract (GI) homeostasis. In the present review, we will discuss the role of a number of dietary nutrients that have been proposed as regulators of inflammation and epithelial barrier function. We will also consider the metabolic function of the microbiota, which is capable of elaborating the diverse nutrients and synthesizing products of great interest. Better knowledge of the influence of dietary nutrients on inflammation and barrier function can be important for the future development of new therapeutic approaches for patients with mucosal barrier dysfunction, a critical factor in the pathogenesis of many GI and non-GI diseases.

Download Full-text

Energy dependence of restitution in the gastric mucosa

AJP Cell Physiology ◽

10.1152/ajpcell.2001.281.2.c430 ◽

2001 ◽

Vol 281 (2) ◽

pp. C430-C438 ◽

Cited By ~ 27

Author(s):

Aaron M. Cheng ◽

Sarah W. Morrison ◽

David X. Yang ◽

Susan J. Hagen

Keyword(s):

Gastric Mucosa ◽

Mitochondrial Respiration ◽

Barrier Function ◽

Metabolic Pathways ◽

Mucosal Barrier ◽

Hypoxic Conditions ◽

Mucosal Barrier Function ◽

Oxidative Respiration

Rapid epithelial repair (restitution) after injury is required to maintain barrier function of the gastrointestinal mucosa and skin and is thought to be a highly ATP-dependent process that would be inhibited under hypoxic conditions. However, little is known about the metabolic pathways required for restitution. Thus, this study was undertaken to evaluate, in vitro, the role of oxidative respiration and glycolysis in restitution after injury. To this end, restitution of the bullfrog gastric mucosa was evaluated under the following conditions: 1) blockade of mitochondrial respiration; 2) blockade of glycolysis; or 3) absence of glucose. The extent of mucosal repair after injury was evaluated by electrophysiology and morphology. Cell migration, repolarization, and the formation of tight junctions after injury occurred during blockade of mitochondrial respiration, whereas the recovery of mucosal barrier function did not. In contrast, glycolytic inhibition completely blocked all aspects of restitution by inhibiting the migration of surface epithelial cells. Restitution occurred in tissues incubated with glucose-free solutions, suggesting that cells contain sufficient glucose (glycogen) to drive glycolysis for many hours. Our results demonstrate that the glycolytic pathway is essential for restitution after injury in the bullfrog gastric mucosa and that all but complete repair of barrier function occurs in the absence of mitochondrial respiration.

Download Full-text

Technical note: fluorescein as an indicator of enteric mucosal barrier function in preruminant lambs

Journal of Animal Science ◽

10.1093/jas/skaa198 ◽

2020 ◽

Vol 98 (7) ◽

Author(s):

Audrey F Duff ◽

Lisa R Bielke ◽

Alejandro E Relling

Keyword(s):

Oral Administration ◽

Intestinal Permeability ◽

Barrier Function ◽

Animal Health ◽

Fluorescein Isothiocyanate ◽

Technical Note ◽

Mucosal Barrier ◽

Published Data ◽

Treatment Groups ◽

Mucosal Barrier Function

Abstract Increased intestinal permeability can be observed during the physiologic stress response and has been linked to suppression of animal health and performance. Previously published data have shown the efficacy of fluorescein isothiocyanate dextran (FITC-d; 4.17 mg/kg) as a marker of enteric inflammation and mucosal barrier function in multiple species. Fluorescein is a smaller, less expensive alternative molecule possessing similar properties. The following two experiments compared FITC-d and fluorescein as potential indicators of intestinal permeability in pre- and postweaned lambs administered daily intramuscular injections of dexamethasone (Dex; 0.1 mg/kg) for 1 wk. Experiment 1 consisted of five preweaned lambs that were placed in one of two treatment groups: fluorescein with Dex (F+Dex) or fluorescein only (F). On day 7, blood was collected before and 1 h after oral administration of fluorescein (50 mg/kg). Experiment 2 included 12 weaned lambs and four treatment groups: F+Dex, F, FITC-d with Dex (Fd+Dex), and FITC-d only (Fd). On day 7, blood was collected before and 2 h after oral administration of FITC-d (4.17 mg/kg) or fluorescein (50 mg/kg). Plasma fluorescence was reported as the ratio between T1h/T0 or T2h/T0 for experiment 1 or 2, respectively. Experiment 1 showed a significant increase in T1h/T0 ratio of F+Dex relative to F lambs (P = 0.05) indicative of increased leaky gut; however, no differences (P = 0.22) were obtained in experiment 2. Results of these experiments suggest fluorescein may serve as a suitable marker of enteric permeability in preruminant lambs, but not in those with functional rumens.

Download Full-text

II. Stress and intestinal barrier function

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.1.g7 ◽

2001 ◽

Vol 280 (1) ◽

pp. G7-G13 ◽

Cited By ~ 245

Author(s):

Johan D. Söderholm ◽

Mary H. Perdue

Keyword(s):

Barrier Function ◽

Clinical Course ◽

Intestinal Barrier ◽

Mucosal Barrier ◽

Intestinal Barrier Function ◽

Barrier Dysfunction ◽

Novel Treatments ◽

Mucosal Barrier Function ◽

Underlying Mechanisms

The influence of stress on the clinical course of a number of intestinal diseases is increasingly being recognized, but the underlying mechanisms are largely unknown. This themes article focuses on recent findings related to the effects of stress on mucosal barrier function in the small intestine and colon. Experiments using animal models demonstrate that various types of psychological and physical stress induce dysfunction of the intestinal barrier, resulting in enhanced uptake of potentially noxious material (e.g., antigens, toxins, and other proinflammatory molecules) from the gut lumen. Evidence from several studies indicates that in this process, mucosal mast cells play an important role, possibly activated via neurons releasing corticotropin-releasing hormone and/or acetylcholine. Defining the role of specific cells and mediator molecules in stress-induced barrier dysfunction may provide clues to novel treatments for intestinal disorders.

Download Full-text