The Influence of CKD on Colonic Microbial Metabolism

Abstract

There is increasing interest in the colonic microbiota as a relevant source of uremic retention solutes accumulating in CKD. Renal disease can also profoundly affect the colonic microenvironment and has been associated with a distinct colonic microbial composition. However, the influence of CKD on the colonic microbial metabolism is largely unknown. Therefore, we studied fecal metabolite profiles of hemodialysis patients and healthy controls using a gas chromatography-mass spectrometry method. We observed a clear discrimination between both groups, with 81 fecal volatile organic compounds detected at significantly different levels in hemodialysis patients and healthy controls. To further explore the differential impact of renal function loss per se versus the effect of dietary and other CKD-related factors, we also compared fecal metabolite profiles between patients on hemodialysis and household contacts on the same diet, which revealed a close resemblance. In contrast, significant differences were noted between the fecal samples of rats 6 weeks after 5/6th nephrectomy and those of sham-operated rats, still suggesting an independent influence of renal function loss. Thus, CKD associates with a distinct colonic microbial metabolism, although the effect of renal function loss per se in humans may be inferior to the effects of dietary and other CKD-related factors. The potential beneficial effect of therapeutics targeting colonic microbiota in patients with CKD remains to be examined.

The cross-talk between the kidney and the gut: implications for chronic kidney disease

“…As far as we know, there is only one study in humans on microbial metabolism in individuals with CKD. Poesen et al [94] investigated fecal metabolite profiles of hemodialysis patients and healthy individuals and observed distinct colonic microbial metabolism between these two groups. They found upregulated generation of p-cresol, indoles, aldehydes, benzenes, furans, and branched-chain, mediumchain, and short-chain fatty acids and a reduced generation of ketones in patients on hemodialysis.…”

“…The clinical impact of these alterations is unknown for the majority of these fecal metabolites. Studies with uremic rats also demonstrated significant differences in fecal metabolite profiles, indicating an important influence of loss of renal function [94,95]. However, in humans, in contrast to rats, when the researchers compared the patients on hemodialysis with household contacts on the same diet, the influence of decreased renal function was inferior to the external factors, such as the diet [94].…”

“…Indeed, it has already been shown in clinical studies that the concentration of these uremic toxins is markedly elevated in all stages of CKD, with a gradual increase as renal function decreases [11,98,99]. Given the importance of colonic metabolism to the composition of the mammalian blood metabolome, it has been proposed that alterations in the colonic metabolism of CKD patients, such as upregulation of both p-cresol and indole generation, can amplify the accumulation of these uremic toxins [94].…”

Urinary metabolites as noninvasive biomarkers of gastrointestinal diseases: A clinical review

“…For example, NMR is able to measure approximately 8% and gas chromatography MS is able to measure approximately 7% of the human urine metabolomes [4] . For the urinary metabolomics, effects of the kidney function as well as the metabolic function of the body which may affect secretion and reabsorption of the circulating metabolites may confound the final results [42] .…”

“…Metabolomics of volatile vs non-volatile compounds is also an important area which should be considered. In addition, the effects of urinary diseases on GI system and microbiota as what has been recently observed in patients with chronic kidney diseases [42] should be taken into account when interpreting urinary metabolomics studies.…”