TLR4 AS THE MARKER OF NON-ALCOHOLIC FATTY LIVER DISEASE PROGNOSIS IN PATIENTS WITH INTESTINAL DYSBIOSIS

Introduction. Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases characterized by the fat accumulation in liver cells and is closely associated with metabolic disorders including obesity and insulin resistance. Considerable interest of researchers is focused on the role of the intestinal microbiome in the NAFLD development and occurrence, since a violation of the normal bacteria balance (dysbiosis) can increase inflammatory processes in the liver. Toll-like receptor 4 (TLR4), which responds to components of the bacterial membrane, is an important marker involved in the development of inflammation and progression of NAFLD.The aim of this study was to determine the level of TLR4 in patients with NAFLD and to find the relationship with gut microbiome components. The study included 152 patients diagnosed with NAFLD and 86 control patients without fatty liver infiltration. General clinical, biochemical, enzyme immunoassay, instrumental and bacteriological methods were used to assess the condition of patients.The results showed that the level of TLR4 in patients with NAFLD was significantly higher than in the control group (2.67±3.05 ng/ml vs. 1.23±0.99 ng/ml). A positive correlation was marked between the TLR4 level and biochemical indicators of inflammation, such as ALT, AST, TG and ALP. It confirms the role of TLR4 in the development of inflammatory processes in NAFLD.In addition, patients with NAFLD showed a significant change in the gut microbiome composition – an increase in the number of Firmicutes phylotype bacteria and a higher level of Firmicutes/Bacteroidetes index, which was in positive correlation with TLR4. Small intestinal bacterial overgrowth (SIBO), which may lead to TLR4 activation, was also marked in 50% of NAFLD patients.Conclusion. The study confirms the role of TLR4 as a marker of the potential tole on NAFLD development and its relationship with intestinal dysbiosis, which could be perspective for the looking of new approaches in the prognosis and treatment of this disease. The microbiome correction and the development of TLR4 inhibitors is an essential way for future investigations as promising therapeutic method.