Intestinal permeability and its role in the pathogenesis of metabolic disorders (metabolic syndrome). Literature review

Abstract

The article highlights the role of intestinal barrier permeability in the pathogenesis of «metabolic diseases» (diabetes, obesity, etc.). It has been shown that normal intestinal microbiota plays an important role in maintaining the integrity of the intestinal epithelial barrier, and disruption of its homeostasis significantly affects not only intestinal permeability, but also systemic inflammatory processes, immune function, insulin resistance, and lipid metabolism. It was determined that the «Western» diet provides the microbiota with the tools necessary to counteract the host’s immune system and that these changes can destroy the intestinal barrier and contribute to the development of metabolic endotoxinemia. The increased intestinal permeability to endotoxin plays a key role in the development of metabolic changes due to increased translocation of bacterial waste products and contributes to the development of both local and systemic low‑grade inflammation. Intestinal microbiota, affecting metabolic processes in adipose tissue and liver due to impaired intestinal permeability, can ultimately affect systemic insulin resistance and glucose dysregulation. Alterations in the relationship between intestinal immune cells and the microbiome result in the aberrant inflammatory distortions, they are associated with intestinal barrier disruption, metabolic disease progression, and insulin resistance. Intestinal immune cells make an additional contribution to the metabolic disease by regulating the bioavailability of gastrointestinal hormones, which subsequently control blood glucose levels and also affect intestinal barrier permeability. Abnormalities in the tight junctions of intercellular connections in the intestine are associated with metabolic and inflammatory diseases. Disturbance of the intestinal barrier function has been confirmed both in animal models of metabolic‑associated diseases and in human studies, and it is indicated that this barrier dysfunction is an important cause of the metabolic syndrome. Data on the effect of lifestyle adjustments (dietary changes, exercise) and therapeutic strategies (metformin, pre‑ and probiotics, bariatric surgery) on intestinal permeability have been presented.