Abstract
Background: Disruption of tight junctions is associated with various inflammatory diseases, including inflammatory bowel syndrome. Tight junctions form a protective barrier throughout the intestinal tract that is central to health. Glyphosate is known to inhibit tight junction function. The aim of this study was to assess the effect of a soil-derived, lignite extract dietary supplement in protecting against glyphosate’s effect on the tight junctions in cell culture. Methods: Small bowel (IEC-6) and colon epithelium (Caco-2) cells were incubated until a stable Transepithelial Electrical Resistance (TEER) was measured. A control and the lignite extract supplement (20% concentration) were placed on the cells and left overnight. These cells were then treated with and without glyphosate at 10 mg/ml. TEER was measured at 30 min. The expression of the tight junctions was determined by immunofluorescent microscopy of the ZO-1 tight junction element before and after overnight incubation, and following glyphosate exposure. Results: TEER increased with the lignite extract on IEC-6 (95%) and Caco-2 (35%) compared to the control. Glyphosate dramatically decreased the TEER in both IEC-6 (80%) and Caco-2 (76%) cells. The lignite extract blocked the glyphosatemediated decrease in TEER. Conclusion: The lignite extract supplement blocked a glyphosate-dependent decrease in TEER in both cell lines. If found efficacious in clinical trials, RESTORE could prove helpful in combating intestinal sensitivities caused by glyphosatemediated tight junction disruption.
Highlights
Intestinal barrier permeability refers to a dysfunction in tight junctions whereby foreign substances are allowed unregulated passage from the apical side to the basolateral side of these epithelial cells
This study aimed to examine how lignite extract influenced the tight junctions of the intestinal barrier system in the presence and absence of glyphosate, measuring the membrane integrity via Transepithelial Electrical Resistance (TEER) of polarized epithelial membranes of normal small bowel epithelium cells (IEC-6) and colon epithelial cells (Caco-2) [14,15,16]
Glyphosate decreased the TEER in IEC-6 cells by 76%, n=4, p
Summary
Intestinal barrier permeability refers to a dysfunction in tight junctions whereby foreign substances (e.g. potential antigens, inorganic compounds, and pathogenic organisms) are allowed unregulated passage from the apical side to the basolateral side of these epithelial cells. Tight junctions are found in all epithelial and endothelial systems such as the nasosinuses, digestive tract, renal tubules, and blood-brain barrier. These tight junctions serve as firewalls, regulating the absorption of water and macronutrients, and participate in immune system response. Tight junctions are comprised of dozens of proteins that aid in this function, including occludin proteins, the Junctional Adhesion Molecules (JAM) family of proteins, and the claudin family of proteins, all of which span the paracellular space. Occludin proteins are responsible for intercellular signaling within the tight junctions, while the JAM proteins aid in trafficking of immune cells to injured or inflamed tissues [1]. The aim of this study was to assess the effect of a soil-derived, lignite extract dietary supplement in protecting against glyphosate’s effect on the tight junctions in cell culture
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