Dysbiosis-Related Advanced Glycation Endproducts and Trimethylamine N-Oxide in Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs.

Keywords: AGEs; RAGE; TMAO; chronic kidney disease; dysbiosis; gut microbiota.

Figure 1

Schematic of the mutual link between gut dysbiosis and uremic toxins in chronic kidney disease (CKD). Excess dietary intake of advanced glycation endproducts (AGEs) affects the composition of the gut microbiome, leading to further uremic toxin production, which results in kidney injury. AGEs deposition in the gastrointestinal tract also disrupts the epithelial barrier, allowing bacterial components and endotoxins to flow into the systemic circulation, which, in turn, leads to other organ damage. The high burdens of uremic toxins such as trimethylamine N-oxide (TMAO) or AGEs are linked to progressive tubular injury and renal fibrosis, which are associated with the development of CKD to end stage renal disease.