The Association between Gut Microbiota and Uremia of Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD)-associated uremia aggravates-and is aggravated by-gut dysbiosis. However, the correlation between CKD severity and gut microbiota and/or their uremic metabolites is unclear. We enrolled 103 CKD patients with stage 1 to 5 and 46 healthy controls. We analyzed patients' gut microbiota by MiSeq system and measured the serum concentrations of four uremic metabolites (<i>p</i>-cresyl sulfate, indoxyl sulfate, <i>p</i>-cresyl glucuronide, and trimethylamine <i>N</i>-oxide) by liquid chromatography-tandem mass spectrometry. Serum concentrations of the uremic metabolites increased with kidney function deterioration. Gut microbial diversity did not differ among the examined patient and control groups. In moderate or higher stage CKD groups, <i>Oscillibacter</i> showed positive interactions with other microbiota, and the proportions of <i>Oscillibacter</i> were positively correlated with those of the uremic metabolites. The gut microbiota, particularly <i>Oscillibacter</i>, was predicted to contribute to pyruvate metabolism which increased with CKD progression. Relative abundance of <i>Oscillibacter</i> was significantly associated with both serum uremic metabolite levels and kidney function. Predicted functional analysis suggested that kidney-function-associated changes in the contribution of <i>Oscillibacter</i> to pyruvate metabolism in CKD may greatly affect the gut environment according to kidney function, resulting in dysbiosis concomitant with uremic toxin production. The gut microbiota could be associated with uremia progression in CKD. These results may provide basis for further metagenomics analysis of kidney diseases.