Microbiome and Cardiovascular Disease in CKD

Abstract

Patients with CKD exhibit a disproportionate burden of cardiovascular mortality, which likely stems from the presence of unique, nontraditional risk factors that accompany deteriorating kidney function. Mounting evidence suggests that alterations to the intestinal microbiome in CKD may serve as one such risk factor. The human intestinal tract is home to >100 trillion micro-organisms made up of a collection of commensal, symbiotic, and pathogenic species. These species along with their local environment constitute the intestinal microbiome. Patients with CKD show intestinal dysbiosis, an alteration of the gut micro-organism composition and function. Recent evidence links byproducts of intestinal dysbiosis to vascular calcification, atherosclerosis formation, and adverse cardiovascular outcomes in CKD. CKD-associated intestinal dysbiosis may also be accompanied by defects in intestinal barrier function, which could further enhance the negative effects of pathogenic intestinal bacteria in the human host. Thus, intestinal dysbiosis, defective intestinal barrier function, and a reduced capacity for clearance by the kidney of absorbed bacterial byproducts may all potentiate the development of cardiovascular disease in CKD. This narrative review focuses on microbiome-mediated mechanisms associated with CKD that may promote atherosclerosis formation and cardiovascular disease. It includes (1) new data supporting the hypothesis that intestinal barrier dysfunction leads to bacterial translocation and endotoxemia that potentiate systemic inflammation, (2) information on the accumulation of dietary-derived bacterial byproducts that stimulate pathways promoting atheromatous changes in arteries and cardiovascular disease, and (3) potential interventions. Despite great scientific interest in and a rapidly growing body of literature on the relationship between the microbiome and cardiovascular disease in CKD, many important questions remain unanswered.

Keywords: Atherosclerosis; Bacteria; Bacterial Translocation; Cardiovascular Diseases; Chronic; Dysbiosis; Endotoxemia; Gastrointestinal Microbiome; Humans; Intestines; Microbiota; Renal Insufficiency; arteries; risk factors; vascular calcification.

Figure 1.

Mechanisms by which microbiome dysbiosis in kidney disease may lead to cardiovascular disease. TMAO, trimethylamine-N-oxide.