Microbiome-metabolome reveals the contribution of gut-kidney axis on kidney disease

Abstract

Dysbiosis represents changes in composition and structure of the gut microbiome community (microbiome), which may dictate the physiological phenotype (health or disease). Recent technological advances and efforts in metagenomic and metabolomic analyses have led to a dramatical growth in our understanding of microbiome, but still, the mechanisms underlying gut microbiome-host interactions in healthy or diseased state remain elusive and their elucidation is in infancy. Disruption of the normal gut microbiota may lead to intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation. Excessive uremic toxins are produced as a result of gut microbiota alteration, including indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide, all implicated in the variant processes of kidney diseases development. This review focuses on the pathogenic association between gut microbiota and kidney diseases (the gut-kidney axis), covering CKD, IgA nephropathy, nephrolithiasis, hypertension, acute kidney injury, hemodialysis and peritoneal dialysis in clinic. Targeted interventions including probiotic, prebiotic and symbiotic measures are discussed for their potential of re-establishing symbiosis, and more effective strategies for the treatment of kidney diseases patients are suggested. The novel insights into the dysbiosis of the gut microbiota in kidney diseases are helpful to develop novel therapeutic strategies for preventing or attenuating kidney diseases and complications.

Keywords: Gut microbiota; Kidney diseases; Metabolome; Microbiome; Probiotics.

Fig. 1

The contribution of the dysbiosis of gut microbiome on various diseases. Gut microbiome alterations and the leaky gut epithelial barrier are associated with chronic kidney disease, heart disease, obesity, non-alcoholic fatty acid disease, rheumatoid arthritis and depression

Fig. 2

Work flows for 16S-based and metagenomics approaches. Microbial community samples contain various species of bacteria and other microorganisms, here indicated by different colors and shapes. After total DNA extraction, the community composition was detected by amplifying and sequencd the 16S rRNA gene. Highly similar sequences are grouped into OTUs, which were labeled by comparison with databases of recognized organisms. OTUs provided the presence/absence, abundance, or phylogenetic diversity. The total metagenomic DNA may be sequenced and compared with function-oriented databases to analyze biomolecular and metabolic functions present in the community. Additionally, sequenced community DNA can be compared with reference genomes. These can identify microbial sequence variants and polymorphisms and provides an alternative method of determining the presence and abundance of specific organisms

Fig. 3

Gut–kidney axis contributes on renal injury through the dysbiosis of gut microbiota and dysregulation of endogenous metabolites. Schematic diagram presented several major metabolites involving in host-gut microbiota communication, originating from synthesis from microbial nutrient conversion, and the subsequent transport and interaction with kidney