Intestinal Microbiota in Type 2 Diabetes and Chronic Kidney Disease

Abstract

Purpose of the Review: Diabetes mellitus is a major cause of kidney disease [chronic kidney disease (CKD) and end-stage renal disease (ESRD)] and are both characterized by an increased risk of cardiovascular events. Diabetes and kidney disease are also commonly associated with a chronic inflammatory state, which is now considered a non-traditional risk factor for atherosclerosis. In the case of type 2 diabetes mellitus (T2DM), inflammation is mainly a consequence of visceral obesity, while in the case of CKD or ESRD patients on dialysis, inflammation is caused by multiple factors, classically grouped as dialysis-related and non-dialysis-related. More recently, a key role has been credited to the intestinal microbiota in the pathogenesis of chronic inflammation present in both disease states. While many recent data on the intestinal microbiota and its relationship to chronic inflammation are available for CKD patients, very little is known regarding T2DM and patients with diabetic nephropathy. The aim of this review is to summarize and discuss the main pathophysiological issues of intestinal microbiota in patients with T2DM and CKD/ESRD. Recent Findings: The presence of intestinal dysbiosis, along with increased intestinal permeability and high circulating levels of lipopolysaccharides, a condition known as “endotoxemia,” characterize T2DM, CKD, and ESRD on dialysis. The hallmark of intestinal dysbiosis is a reduction of saccharolytic microbes mainly producing short-chain fatty acids (SCFA) and, in the case of CKD/ESRD, an increase in proteolytic microbes that produce different substances possibly related to uremic toxicity. Summary: Dysbiosis is associated with endotoxemia and chronic inflammation, with disruption of the intestinal barrier and depletion of beneficial bacteria producing SCFAs. T2DM and CKD/ESRD, whose coexistence is increasingly found in clinical practice, share similar negative effects on both intestinal microbiota and function. More studies are needed to characterize specific alterations of the intestinal microbiota in diabetic nephropathy and to assess possible effects of probiotic and prebiotic treatments in this setting.