Intestinal microbiota as a fundamental basis for homeostasis, general pathology and aging

Abstract

Intestinal microbiota is a kind of satellite organ that performs digestive and protective functions, a supplier of molecules vital for homeostasis processes, involved in metabolic processes and determining the activity level of adaptive systems, including immunity. Immunity works both for and against the host, which is predetermined by the very nature of adaptive immunity and its interaction with the innate link of the immune system. The key element of this interaction is endotoxin molecules, or lipopolysaccharides, the concentration of which in the general bloodstream determines the activity level of adaptive (mediated by innate) immunity, which operates in a stochastic mode. This provides both antitumor protection and self-destruction of the body based on autoimmune damage. Over the past 35 years, there has been a powerful breakthrough in the field of understanding the mechanisms of interaction between the intestinal microbiota and the host organism. Interesting data have been obtained and published that have not yet been fully systematized and understood. The methodology for studying the biological role of lipopolysaccharides in clinical settings developed by Russian scientists was based on the ability of agents for reducing their blood levels to increase the effectiveness of the treatment and preventive process. In particular, it made it possible to establish the involvement of the lipopolysaccharide factor in the pathogenesis of a number of diseases. The phenomenon of systemic endotoxinemia discovered by Russian researchers is a process of controlling the activity of adaptive systems (including the immune system) with the participation of the hypothalamic-pituitary-adrenal system by means of intestinal endotoxins. We see the following issues for wide discussion in the clinical community: (1) determining the directions for finding agents for normalizing systemic endotoxinemia indicators as the basis of preventive medicine, including pro- and prebiotics, entero- and hemosorbents, hepatoprotectors, immunopreparations, chaotropic effects (plasmapheresis, blood irradiation); (2) clinical and experimental models for studying diseases associated with intestinal microbiota; (3) creation of a research protocol to establish the age range of integral indicators of systemic endotoxinemia (the level of lipopolysaccharides and the activity of antiendotoxin immunity that resists endotoxin aggression); (4) ways to understand the mechanisms of development of endotoxin tolerance accompanying aging and its overcoming.