Мелатонин как перспективный фактор коррекции кишечного микробиома при воспалительных заболеваниях кишечника

Abstract

Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn's disease. The etiology and pathogenesis of IBD remain unclear, the most common hypothesis being that an abnormal immune response against the gut microbiome is triggered by environmental factors in genetically predisposed individuals. The disadvantages of first-line therapy for IBD are the occurrence of side effects in more than 30% of patients. In this regard, the development of new safe drugs that act mainly locally is relevant. The aim of the work is to analyze current data on the mechanisms of action, effects on the intestinal microbiome of melatonin in the context of possible use in IBD. Melatonin (MT) is a biologically active substance, synthesized in the body from tryptophan, and realizes its effects through MT-dependent and MT-independent receptors located in the cell membrane and nucleus. MT is involved in the regulation of circadian rhythms, has antioxidant and immunomodulatory effects. In experimental modeling of IBD and in clinical conditions, MT reduces the severity of the inflammatory process in the wall of the colon by interrupting the processes of lipid peroxidation and inactivation of free radicals, as well as by acting through specific receptors on the function of blood cells of lymphoid organs. MT in IBD leads to a qualitative and quantitative change in the intestinal microbiome, elimination of signs of dysbiosis, an increase in the number of short-chain fatty acid producers - Actinomycetota (Actinobacteria) and a decrease in the number of bacteria that increase the permeability of the intestinal barrier - Bacteroidota (Bacteroidetes). Presumably, MT has a bacteriostatic effect by binding free iron and acting on the NF-kB and STAT1 signaling pathways, which may be a factor in the correction of colon dysbiosis in IBD. Data on the effect of MT on the composition of the intestinal microbiome are a prerequisite for further preclinical studies and the possible use of melatonin in IBD in clinical practice.