Microbiome in Chronic Kidney Disease

Abstract

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human's body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD.

Keywords: chronic kidney disease; dialysis; microbiome; microbiota; transplantation.

Figure 1

Relationship between kidney-gut axis, gut microbiome and implications in chronic kidney disease (CKD). As renal function declines, urea accumulates in the bloodstream and diffuses into the gut lumen. Urea is converted to ammonia and subsequently to ammonium hydroxide; this causes disruption of the epithelial barrier and increases the gut permeability (red arrows above inscription “kidney”). Certain bacteria (green double arrow) metabolize urea and other diet products, leading to overproduction of protein bound uremic toxins, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS) and Trimethylamine-N-Oxide (TMAO) (green arrow). Moreover, the production of anti-inflammatory short-chain fatty acids (SCFA) is reduced. The accumulation of uremic toxins (blue arrow) is associated with renal, cardiovascular (CV) and other implications (black arrows). Renal fibrosis (left red arrow) and local inflammation (left blue arrow) promote progression of CKD. So, a vicious cycle in kidney-gut axis is formed (curved arrows). Each color represents different organ or category: red, kidney; green, gut; purple, liver; blue, blood; grey, cardiovascular implications; brown, other implications. ESRD, end stage renal disease; TNF-α, tumor necrosis factor α; IL-6, interleukin 6.