Changes in the composition of the gut microbiota and content of microbial-derived uremic toxins in patients undergoing hemodialysis

Abstract

Recent data highlight a significant role of the gut microbiota in the pathogenesis of chronic kidney disease, particularly in its terminal stage. However, little is known about the features of intestinal dysbiosis in people undergoing programed hemodialysis. Changes in the intestinal microbiota and blood levels of uremic toxins of microbial origin in patients with terminal renal insufficiency receiving hemodialysis were analyzed. This cross-sectional study included 80 patients receiving hemodialysis and 20 individuals with normal kidney function. The state of the microbiocenosis of the colon was studied using a polymerase chain reaction with a commercial set Colonoflor 16 (premium) manufactured by Alfalab (Russia). Serum levels of trimethylamine and its metabolite trimethylamine-N-oxide were determined by liquid chromatography/mass spectrometry. The concentrations of indoxyl sulfate and p-cresyl sulfate were evaluated by enzyme immunoassay according to the instructions of a commercial kit. In patients undergoing programed hemodialysis, increased colonization of enterococci was combined with the reduction of lacto and bifidophlora, E. coli, ruminococci, bacteria producing short-chain fatty acids (Faecalibacterium prausnitzii, Eubacterium rectale, Roseburia inulinivorans, and Blautia spp.) and microorganisms involved in maintaining the integrity of the intestinal barrier (Bacteroides thetaomicron and Akkermansia muciniphila). In addition, high titer levels of representatives of opportunistic and even pathogenic flora were often found in this group. Intestinal dysbiosis in patients undergoing programed hemodialysis was accompanied by a significant increase in the concentration of uremic toxins in the blood. Compared with individuals with normal renal function, the trimethylamine level in patients undergoing programed hemodialysis was increased 22 times; trimethylamine-N-oxide, 23 times; indoxyl sulfate, 21 times; and p-cresyl sulfate, 5 times. Thus, patients receiving hemodialysis exhibited pronounced pathological changes in intestinal microbiocenosis, accompanied by a significant increase in serum levels of uremic toxins of microbial origin.