Intestinal permeability and its role in the pathogenesis and progress of non-alcoholic fatty liver disease. Review

Abstract

Non‑alcoholic fatty liver disease (NAFLD) is a topical problem for the medicine worldwide, and its association with an «unhealthy» lifestyle and metabolic disorders is well established. The important role of dysbiosis of the intestinal microbiota in the NAFLD pathogenesis and the functioning of the intestine‑liver axis is emphasized. Data on the structure and functioning of the intestinal barrier in physiological conditions are presented. It has been proven that the presence of dysbiotic changes in the microbiota plays an important role in the disruption of the barrier function of the gastrointestinal tract, which in turn increases the level of physiological translocation of both bacteria and their toxins and their life products. Part of these harmful products comes to the liver through the portal vein (endotoxinemia). The antigens’ overload contributes to the development and progression of NAFLD (up to liver cirrhosis). The intestinal barrier is emphasized to be dynamic and sensitive to changes occurring in the intestine. The increased intestinal permeability and bacterial overgrowth syndrome (which is a source of increased endotoxemia) is observed in patients with NAFLD more frequently than in healthy subjects. Number of studies have revealed that the degree of intestinal permeability in NAFLD patients correlated with the steatosis severity. The factors that most significantly affect intestinal permeability in patients with NAFLD include microbial environment, bile acids, levels of fecal short‑chain fatty acids (mainly butyrate), the metabolism of the essential aromatic amino acid tryptophan, as well as the nature of nutrition, alcohol intake, medicinal preparations, stress, and level of physical activity, which act either directly or through the induction of intestinal microbiota dysbacteriosis. The increased intestinal permeability and its consequence — bacterial translocation, are noticed to be involved in the development of such complications as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, hepatocellular carcinoma.