Microbiome in Chronic Kidney Disease (CKD): An Omics Perspective

Abstract

Chronic kidney disease (CKD) is predominant in 10% of the world's adult population, and is increasingly considered a silent epidemic. Gut microbiota plays an essential role in maintaining host energy homeostasis and gut epithelial integrity. Alterations in gut microbiota composition, functions and, specifically, production of metabolites causing uremic toxicity are often associated with CKD onset and progression. Here, we present the latest omics (transcriptomics, proteomics and metabolomics) studies that explore the connection between CKD and gut microbiome. A review of the available literature using PubMed was performed using the keywords "microb*", "kidney", "proteom", "metabolom" and "transcript" for the last 10 years, yielding a total of 155 publications. Following selection of the relevant studies (focusing on microbiome in CKD), a predominance of metabolomics (n = 12) over transcriptomics (n = 1) and proteomics (n = 6) analyses was observed. A consensus arises supporting the idea that the uremic toxins produced in the gut cause oxidative stress, inflammation and fibrosis in the kidney leading to CKD. Collectively, findings include an observed enrichment of Eggerthella lenta, Enterobacteriaceae and Clostridium spp., and a depletion in Bacteroides eggerthii, Roseburia faecis and Prevotella spp. occurring in CKD models. Bacterial species involved in butyrate production, indole synthesis and mucin degradation were also related to CKD. Consequently, strong links between CKD and gut microbial dysbiosis suggest potential therapeutic strategies to prevent CKD progression and portray the gut as a promising therapeutic target.

Keywords: CKD; gut microbiota; omics; therapeutic targets; uremic toxins.

Figure 1

The complex bidirectional interactions of the gut-kidney axis. Gut microbiota produce proteins and metabolites acting as uremic toxin precursors which are converted into uremic toxins in the liver and are normally excreted by the kidneys in urine. External factors such as diet, obesity, diabetes, hypertension, proteinuria and cardiovascular disease (CVD) cause CKD, as measured by a reduced GFR and/or increased urea concentrations. In the case of CKD, the microbially produced uremic toxins accumulate in the host system, leading to enhanced oxidative stress, inflammation and/or fibrosis which may have a detrimental effect on the functionality of gut microbiota and other host organs like heart and kidneys, forming a vicious cycle.

Figure 2

Workflow followed for the retrieval of the presented omics studies associated with gut microbiota and CKD. *—keywords were used with “*” to perform a broader search, irrespective of their use in multiple forms, for example plurals. **—additional keywords used for the search include “renal”, “gut”, “*omics”, etc., but yielded in most extent overlapping results.

Figure 3

State-of-the-art omics experimental study. The different types of samples used in an omics study of relevance to this review are fecal and cecal contents, serum, plasma, urine, kidney and aorta tissue samples. After the samples are prepared following a chemical protocol in the laboratory, the extracted proteins, RNA or metabolites are subjected to the respective -omics analysis, performed by state-of-the-art instruments like LC-MS, high throughput sequencer or nuclear magnetic resonance (NMR) spectroscopy. The data collected are then subjected to further bioinformatic analysis targeting their integration into molecular pathways and the better understanding of the system.