Pathogenetic relationship of intestinal microbiota and microbial metabolome with chronic kidney diseases

The modern concept of the “pathogenetic intestine–kidney axis” reflects the connection between the state of the gut microbiome and the development of chronic kidney disease (CKD). Intestinal dysbiosis, caused by various factors, manifests itself as a change in the quantitative and qualitative composition of the microflora, with disruption of production of its metabolites, which are involved in regulating important metabolic and energy processes in the body. Among the most significant of these are short-chain fatty acids (SCFAs), which are formed as a result of bacterial fermentation of indigestible dietary fiber. The effects mediated by SCFAs have not only a local but also a systemic impact. By affecting the permeability of the intestinal mucosa and its peristalsis, the secretion of intestinal hormones, immune activity, and other regulatory mechanisms—including the maintenance of blood pressure—SCFAs ensure the normal functioning of individual organs and systems. In CKD, disruption of the intestinal microbiocenosis is associated with a decrease in the diversity of microorganisms, including commensal ones, which leads to a reduction in the production of key SCFAs and causes disruptions in lipid and carbohydrate metabolism, immune regulation, and the development of inflammatory processes. Against this backdrop, in patients suffering from CKD, as kidney function declines, there is an accumulation of other products of bacterial metabolism, such as indole derivatives, phenols, and others, which, due to their toxic effect, contribute not only to further kidney damage but also to the accelerated development of atherosclerosis and the emergence of cardiovascular complications. The review analyzes and systematizes the results of studies conducted by domestic and foreign authors on the state of the gut microbiome, the spectrum of SCFAs, and other metabolites in patients suffering from CKD, since this problem is relevant not only in terms of clarifying the mechanisms of pathogenesis of this condition but also in assessing the potential of therapeutic approaches aimed at slowing the progression of renal function loss by restoring the normal composition of the gut microbiota.