Intestinal microbiota and diabetic kidney diseases: the Role of microbiota and derived metabolites inmodulation of renal inflammation and disease progression

Diabetic kidney disease (DKD) represents a growing public health burden and is the leading cause of end-stage kidney diseases. In recent years, host-gut microbiota interactions have emerged as an integral part for host homeostasis. In the context of nephropathies, mounting evidence supports a bidirectional microbiota-kidney crosstalk, which becomes particularly manifest during progressive kidney dysfunction. Indeed, in chronic kidney disease (CKD), the "healthy" microbiota structure is disrupted and intestinal microbes produce large quantities of uremic solutes responsible for renal damage; on the other hand, the uremic state, fueled by reduced renal clearance, causes shifts in microbial metabolism and composition, hence creating a vicious cycle in which dysbiosis and renal dysfunction are progressively worsened. In this review, we will summarize the evidence from clinical/experimental studies concerning the occurrence of gut dysbiosis in diabetic and non -diabetic CKD, discuss the functional consequences of dysbiosis for CKD progression and debate putative therapeutic interventions targeting the intestinal microbiome. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).