The article presents modern concepts on the role of the intestinal microbiome in the pathogenetic mechanisms of the development of metabolically associated diseases. The history of endotoxin discovery has been described. The multifaceted endotoxin properties have been established in relation to both infectious and non‑infectious pathology. A stress theory of the regulation of intestinal lipopolysaccharide intake into the general bloodstream is described, and research data supporting the hypothesis are presented. The data on the physiological role of lipopolysaccharide and data on its characteristics depending on age, stress and physical activity are presented. The main mechanisms of the development of endotoxemia are shown, including the role of the disturbance of eubiosis of the intestinal microbiome and an increase in intestinal permeability. The role of the liver in the primary inactivation of endotoxin in healthy individuals has been elucidated. The role of lipids in the transport of intestinal lipopolysaccharide is indicated. The concepts of «endotoxin aggression» and «metabolic endotoxin aggression» are described. The role of a high‑fat diet in the development of endotoxemia, including through the development of dysbiosis, was revealed. The results of experimental studies on the administration of lipopolysaccharide to laboratory animals are described — the administration of endotoxin induces an increase in the level of pro‑inflammatory cytokines. The mechanisms of its interaction with Toll‑like receptors and the consequences of this interaction expressed in the potentiation of chronic inflammation in the liver tissue are presented. The role of endotoxin aggression in the induction of low grade inflammation in obese patients and the relationship with changes in the intestinal microbiome have been disclosed. The effects of lipopolysaccharide in the development of insulin resistance and type 2 diabetes mellitus are shown. The data of studies on the role of endotoxinemia in the development of non‑alcoholic fatty liver disease with the specification of the mechanism of interaction of lipopolysaccharide with liver cells and the progression of its course with the development of steatohepatitis and fibrosis.