Intestinal Permeation and Gastrointestinal Disease

Abstract

The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier. A variety of specific and nonspecific mechanisms are in operation to establish the host barrier; these include luminal mechanisms and digestive enzymes, the epithelial cells together with tight junctions in between them, and the gut immune system. Disruptions in the gut barrier follow injury from various causes including nonsteroidal anti-inflammatory drugs and oxidant stress, and involve mechanisms such as adenosine triphosphate depletion and damage to epithelial cell cytoskeletons that regulate tight junctions. Ample evidence links gut barrier dysfunction to multiorgan system failure in sepsis and immune dysregulation. Additionally, contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohn's disease, celiac disease, food allergy, acute pancreatitis, non-alcoholic fatty liver disease, and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism.

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats

“…Although the link between activation of the GI immune system and pancreatic beta cell destruction is incompletely understood, current knowledge suggests that antigens are presented to the gut-associated lymphoid tissue (GALT) through the paracellular pathway (6). Lymphocytes are known to circulate between GALT, lymph nodes, and other tissues.…”

“…The specific cells involved in this immune response include antigen-presenting cells, T and natural T killer lymphocytes (NK), B lymphocytes, and plasma cells (5). These cells lie in close proximity to the intestinal epithelial barrier and facilitate immune responsiveness, especially in the presence of elevated intestinal epithelial permeability (6). Recent reports suggest that quantitative and͞or qualitative deficiencies in a subset of NK cells occur in several autoimmune diseases, including type 1 diabetes (T1D) (7) and celiac disease (CD) (8).…”

“…Recent reports suggest that quantitative and͞or qualitative deficiencies in a subset of NK cells occur in several autoimmune diseases, including type 1 diabetes (T1D) (7) and celiac disease (CD) (8). These cells play a pivotal role in the maintenance of immune tolerance by down-regulating the immune response to foreign antigens when they gain access beyond the intestinal mucosal barrier (6). Recent studies in humans and in animal models have linked the presence of increased intestinal permeability to the occurrence of autoimmune diseases (8)(9)(10)(11)(12)(13).…”

Integrative medicine and leaky gut syndrome

“…'Leaky gut' is the name given for this increase in intestinal permeability and is commonly seen in patients presenting with inflammatory bowel disease, 5 food allergies and intolerances 6 and celiac sprue. 7 Intestinal permeability may be the main cause of sensitivity to particular types of food. In a study authored by Ventura, a statistically significant difference was found in intestinal permeability in subjects with food allergy or hypersensitivity compared to controls, and the results indicated that the worse the permeability, the more serious the clinical symptoms.…”

Combination of allopurinol and hyperbaric oxygen therapy: A new treatment in experimental acute necrotizing pancreatitis?

“…Translocation of enteric bacteria is the most important cause of infection in the pancreatic tissue, and subsequent events such as sepsis and related complications [2,3] . Currently, several treatment options have been proposed for the septic complications of AP.…”