A substantial body of evidence points to the importance of renal filtration and the elimination of microbiome-derived metabolites. Chronic kidney disease can lead to renal failure, which can have detrimental consequences for the elimination of microbiome metabolites. Specifically, p-cresyl sulfate and indoxyl sulfate are cometabolites between human metabolism and microbiome fermentation. Kidney failure or loss of renal function can lead to retention of these metabolites, and they can induce toxic harm by remaining in systemic circulation. While there has been significant interest in this field, much is unknown regarding CKD’s influence on microbiota function and metabolism. Researchers in Belgium sought to address this and identify what role CKD would have on the microbiota metabolism in the colon in patients on hemodialysis.
The experimenters examined 20 patients on hemodialysis. These fecal metabolites profiles of these patients were compared to 20 healthy controls using gas chromatography-mass spectrometry. Initial observations revealed that healthy controls had a significantly higher number of volatile organic compounds (VOCs) – an indicator of microbiota metabolism - as compared to the patients on hemodialysis. After adjusting the data for statistical confounders and discriminating VOCs between groups, the researchers determined that 81 individual VOCs were significantly different between hemodialysis patients and healthy controls. Consistent with previous findings and known clinical conditions, both p-cresol and indole were significantly upregulated in hemodialysis patients. A major confounder in this study is diet, as hemodialysis patients are on a very restricted diet, and as we know, dietary intake impacts microbiome composition and metabolism. The researchers conducted the same analysis with the hemodialysis patients with household contacts who were on the same diets. Interestingly, no significant difference in VOCs was observed between groups.
The researchers demonstrated that CKD patients on hemodialysis experience an altered microbiota metabolism; however, dietary influence may be driving this effect rather than loss of renal function. It was good to see the researchers included the household controls, as this evidence suggests renal function by itself may not have direct impacts on gut microbiota function. Regardless, much of the CKD-microbiome research to this date has focused on the microbiome’s role in CKD or CKD-mediated downstream maladies. It was interesting to see a study that took the opposite approach, as we know microbiome health is important for homeostatic mechanisms that maintain a healthy body.