The gut-kidney-heart axis in chronic kidney disease

The recent explosion of scientific interest in the gut microbiota has dramatically advanced our understanding of the complex pathophysiological interactions between the gut and multiple organs in health and disease. Emerging evidence has revealed that the gut microbiota is significantly altered in patients with chronic kidney disease (CKD), along with impaired intestinal barrier function. These alterations allow translocation of various gut-derived products into the systemic circulation, contributing to the development and progression of CKD and cardiovascular disease (CVD), partly mediated by chronic inflammation. Among potentially toxic gut-derived products identifiable in the systemic circulation, bacterial endotoxin and gut metabolites (e.g., p-cresyl sulfate and trimethylamine-N-oxide) have been extensively studied for their immunostimulatory and atherogenic properties. Recent studies have also suggested similar biological properties of bacterial DNA fragments circulating in the blood of patients with CKD, even in the absence of overt infections. Despite the accumulating evidence of the gut microbiota in CKD and its therapeutic potential for CVD, the precise mechanisms for multidirectional interactions between the gut, kidney, and heart remain poorly understood. This review aims to provide recent evidence on the associations between the gut microbiota, CKD, and CVD, and summarize current understanding of the potential pathophysiological mechanisms underlying the "gut-kidney-heart" axis in CKD.