Intestinal microbiota and metabolically associated steatotic liver disease: current understanding of the problem. Review

Cross‑interaction of microbes, microbial products, and the intestinal barrier are components of the so‑called «intestine‑liver axis», as the liver and intestines have a close two‑way relationship. In patients with metabolically associated steatotic liver disease (MASLD), significant characteristic changes in the intestinal microbiome are observed, in particular, the growth of gram‑negative bacteria, which contributes to the formation of a pro‑inflammatory status (primarily due to endotocins) and disruption of metabolic processes, while an increase in Bacteroides and Ruminococcus and a decrease in Prevotella are associated with severe stages of liver fibrosis. Intestinal microbiota modulates the pool of bile acids thereby affecting metabolic homeostasis and pro‑inflammatory processes. Dysbiosis associated with MASLD is characterized by an excess of bacteria — producers of secondary bile acids, which are one of the factors in the progression of metabolically associated steatohepatitis. In addition, dysbiosis leads to increased production of short‑chain fatty acids, which promotes gluconeogenesis, synthesis and accumulation of toxic lipids in the liver and, accordingly, the development and progression of MASLD. But liver function disorders connected with dysbiosis are associated not only with intestinal bacteria, but also with fungi and viruses. According to the results of recent studies, MASLD is associated with a significant diversity of the mycobiome and has certain differences in the progression of the disease depending on the degree of liver inflammation and the stage of fibrosis. Chronic hyperproduction of endogenous ethanol (Klebsiella pneumoniae, Escherichia, Candida, etc.) is an important factor in the pathogenesis of MASLD, as it disrupts glucose and lipid metabolism, contributing to the formation of liver steatosis and steatohepatitis. Ultrastructural and functional changes of mitochondria are recognized determinants in the pathogenesis of MASLD. Mitochondria and intestinal microbiota have a bidirectional relationship: microbiota supplies metabolites for mitochondrial metabolism and redox homeostasis, and the development of dysbiosis contributes to oxidative stress and proinflammatory status — key factors in the development of metabolically associated steatohepatitis. Mitochondria can also modulate intestinal microflora by affecting the permeability of the intestinal barrier. The data presented in the article expand our knowledge about the interaction of the liver and the intestine and inspire the development of new promising therapeutic approaches to the treatment of MASLD, which involve a synergistic effect on the intestinal microbiota, microbiome, virome, and mitochondrial function.