Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease

Abstract

The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression.

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

“…A growing number of manufactured and naturally-occurring elements in processed foods and mono-crop farming are being implicated in tight junction damage [20]. In the developed world, the unintentional chronic stimulation of zonulin-mediated intestinal permeability from food elements, such as the gluten-derived peptides that include the PT-gliadin used in this study, compromises tight junction integrity and leads to unregulated absorption of organic and inorganic material.…”

“…Some of these substances include the bioflavonoid quercetin and indole, butyrate, nicotine, the amino acid L-glutamine, the mineral zinc, the pharmaceutical compound and zonulin-inhibitor larazotide, and now the novel lignite extract studied here [19][20][21][22][23][24][25][26][27][28][29][30]. The lignite extract supplement has unique biologic effects among these reported compounds in both the speed of response in the TEER functional analysis of the tight junction, which occurred within 60 min from introduction to the membranes, and the extent of the response in regard to tight junction protein expression as seen by immunofluorescence.…”

Investigation of Different Formulation Approaches to Enhance Oral Bioavailability of Paromomycin

“…Terpenes like menthol were shown to increase the permeability either by increasing the fluidity or by disruption of tight junctions of intestinal membrane [22] . Fatty alcohols like Gelucire 44/14, Capmul MCM C8, Captex, Acconon, Labrafil and Maisine were shown to increase the permeability by disrupting the intestinal barrier [22][23][24] . Solutol HS-15, a non-ionic surfactant was reported to increase the permeability by disrupting the membrane structure and/or increasing the membrane fluidity [25] .…”

GUT-the Trojan Horse in Remote Organs’ Autoimmunity

“…Multiple sclerosis, type 1 diabetes, inflammatory bowel diseases (mainly Crohn's disease), systemic lupus erythematosus, primary biliary cirrhosis, myasthenia gravis, autoimmune thyroiditis, autoimmune hepatitis, rheumatic diseases , bullous pemphigoid, and celiac disease (CD) are several examples [1,[3][4][5]. Geoepidemiologically, their relationship to socioeconomic status, their rapid increase in developed countries, the selected populations migrating from under developed to the westernized territories and the relatively low concordance rate for most of the ADs between monozygotic twins, indicate some form of environmental impact, rather than long-term genetic influences which are driving these recent evolutionary processes [1][2][3][4][5][6]. Such rapid change invokes a causal role for environmental factors associated with modern life-improved public health, use of antibiotics in medicine and agriculture, and changes in diet.…”

“…It seems that the nutritional exposome is far from explaining human reactome. Most recently, the hypothesis that changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of ADs, was forwarded [3]. 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.…”