Chronic kidney disease not only eventually leads to end-stage renal disease requiring dialysis, but also significantly increases the incidence and mortality of cardiovascular disease.In recent years, it has also been revealed that increased blood levels of trimethylamine-N-oxide (TMAO), a metabolite derived from the intestinal flora, are a major risk factor for cardiovascular disease and increase the mortality rate of patients with chronic kidney disease. It has become.Therefore, lowering blood TMAO levels is considered to be a new target for the treatment and prevention of cardiorenal syndrome.

　So far, the research group of Professor Abe et al. Has continued to research and develop new treatment methods for kidney disease, focusing on the intestinal environment and metabolites derived from the intestinal flora.This time, the research group used linaclotide, which is a therapeutic drug for constipation, as a drug that changes the intestinal environment, and investigated the therapeutic effect on kidney disease.

　As a result, administration of linaclotide to renal insufficiency mice improved renal function and tissue damage and suppressed the progression of renal disease.In addition, the blood concentration of TMAO decreased, and the progression of myocardial fibrosis and the increase in blood biomarker levels observed in renal failure mice were suppressed.In addition, gut microbiota analysis showed that administration of linaclotide reduced the proportion of certain gut microbiota.It became clear that this change was associated with a decrease in TMAO.

　The results of this study indicate that reducing TMAO by improving the intestinal environment helps prevent and treat cardiorenal syndrome through the intestinal-heart-renal link, and linaclotide may be a candidate drug. ..

Paper information:[Nephrology Dialysis Transplantation] The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease