Leaky Gut and Autoimmune Diseases

Abstract

Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

“…Patients with, in particular, overt CeD appear also to develop autoreactivity to GP2 [95] (Roggenbuck, unpublished results). In CeD, anti-GP2 IgA correlated with CeD-specific antitransglutaminase and antideamidated gliadin IgA giving support to the hypothesis that a leaky gut induces or facilitates this break of tolerance [97]. Excluding patients with CeD and UC, the specificity of anti-GP2 for CrD in comparison with non-intestinal disease controls is about 98%.…”

GUT-the Trojan Horse in Remote Organs’ Autoimmunity

“…In fact, glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles, extensively and increasingly used by the food processing industries, are breaches of the intestinal tight junction integrity. The leaky gut as discussed below, is a well-known pathway that drives not only allergy, but also systemic autoimmunity [10].…”

“…Is it a cause, consequence or coevolutional phenomenon? [10,[27][28][29]. Data is accumulating that intestinal luminal environmental factors might perturbate the regulatory mechanisms of the tight junction, resulting in a leaky gut thus breaking equilibrium between tolerance and immunity to nonself-antigens.…”

Protection against Gluten-mediated Tight Junction Injury with a Novel Lignite Extract Supplement

“…These tight junctions function as selective gatekeepers that regulate the absorption of macronutrients, and compose a frontline of defense. The increased gut permeability that results from tight junction dysfunction is increasingly recognized as an early step in the pathogenesis of many acute and chronic inflammatory diseases, including celiac disease and inflammatory bowel disease (Crohn's Disease and ulcerative colitis) [1][2][3][4][5][6]. The chronic inflammatory underpinnings of these conditions point to the chronic immune system activation of the gastrointestinal-associated lymphoid tissue that becomes exposed with tight junction dysfunction.…”