BioAcyl Corp
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Aleman, R. S., Moncada, M., & Aryana, K. J. (2023). Leaky gut and the ingredients that help treat it: A review. Molecules, 28(619). Added by: Dr. Enrique Feoli (10/08/2026, 09:51) Last edited by: Dr. Enrique Feoli (10/08/2026, 20:08) |
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| Resource type: Journal Article Published DOI: 10.3390/molecules28020619 ID no. (ISBN etc.): 1420-3049 BibTeX citation key: Aleman2023 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Microbiota on immunity Creators: Aleman, Aryana, Moncada Collection: Molecules |
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| Abstract |
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The human body is in daily contact with potentially toxic and infectious substances in the gastrointestinal tract (GIT). The GIT has the most significant load of antigens. The GIT can protect the intestinal integrity by allowing the passage of beneficial agents and blocking the path of harmful substances. Under normal conditions, a healthy intestinal barrier prevents toxic elements from entering the blood stream. However, factors such as stress, an unhealthy diet, excessive alcohol, antibiotics, and drug consumption can compromise the composition of the intestinal microbiota and the homeostasis of the intestinal barrier function of the intestine, leading to increased intestinal permeability. Intestinal hyperpermeability can allow the entry of harmful agents through the junctions of the intestinal epithelium, which pass into the bloodstream and affect various organs and systems. Thus, leaky gut syndrome and intestinal barrier dysfunction are associated with intestinal diseases, such as inflammatory bowel disease and irritable bowel syndrome, as well as extra-intestinal diseases, including heart diseases, obesity, type 1 diabetes mellitus, and celiac disease. Given the relationship between intestinal permeability and numerous conditions, it is convenient to seek an excellent strategy to avoid or reduce the increase in intestinal permeability. The impact of dietary nutrients on barrier function can be crucial for designing new strategies for patients with the pathogenesis of leaky gut-related diseases associated with epithelial barrier dysfunctions. In this review article, the role of functional ingredients is suggested as mediators of leaky gut-related disorders.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
| Notes |
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Adherent junctions regulate adhesion between adjacent cells through transmembrane adhesion molecules of the catenins and protein complexes associated with the actin cytoskeleton. The AJs are located on the lateral membrane below the TJs and are necessary to assemble and maintain tight joints. E-cadherin is among the isoforms of cadherin in epithelial tissues and participates in cellular processes, cell proliferation, the establishment of cell polarity, and remodeling of the actin cytoskeleton [26]. Desmosomes are intercellular junctions composed of desmocolins, desmoglein, and cadherins. These intercellular junctions can also act as intracellular signaling mediums [26]. Gap junctions are made up of six transmembrane proteins called connexins. They allow communication between cells, performing an essential function in the development, growth and differentiation of epithelial cells [12]. For cells to form an epithelium, they need to be attached to the membrane by intercellular junctions. These junctions are classified into three groups (Figure 4): intercellular junctions, anchor junctions, and communicating junctions [20,21]. Tight junction proteins (TJs) are generated by assembling multiple proteins located in the apical part of the epithelium between neighboring cells and control the permeability of the transport pathway paracellular, restricting the passage of ions and solutes. In addition, they maintain the polarity of the epithelial cells by preventing the passage of molecules (lipids and proteins) from the apical membrane to the basolateral and vice versa, so the TJs have a very important function in the establishment of the intestinal barrier. They consist of integral transmembrane proteins that include occludin, tricellulin, claudins, and junctional adhesion molecules (JAMs) and peripheral proteins known as zonula occludens (ZO-1, ZO-2, ZO-3), which bind to actin filaments (Figure 4) [22,23]. Tight junction proteins are highly regulated, which is critical for maintaining the integrity of the normal barrier. The epithelial cells of the intestine proliferate and renew rapidly, and the tight junction proteins must be regulated to avoid any deleterious effect on the integrity of the barrier. The tight junction proteins can adapt to the different demands of the cells, sealing, opening, and maintaining paracellular transport under different physiological and pathological conditions [24]. Regulation is complex and performed by multiple proteins and signaling pathways, such as protein kinases C, A, and G (PKC, PKA, and PKG), phosphatase, myosin light-chain kinase (MLCK), mitogen-activated protein kinases (MAPK), and the phosphatidylinositol-3 kinase pathway (B/Akt, PI3K/Akt). Phosphorylation of occludin is responsible for opening and sealing tight junctions [3]. The plasticity of TJs is essential for gastrointestinal functions, epithelial renewal, and morphogenesis. Under normal physiological conditions, tolerance and homeostasis are maintained with intestinal permeability controlled. However, any defects in the barrier with the TJs open in a deregulated and prolonged way can allow the passage of antigens from the diet or bacteria, a situation known as leaky gut syndrome [25].
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Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
