Kidney Function Modulates Gut Microbial Metabolism

Growing evidence suggests that chronic kidney disease (CKD) profoundly disrupts gut microbiome and its activity. This study explores how CKD affects colon microbial metabolism, focusing on (1) the representativeness of fecal metabolomics, (2) saccharolytic and proteolytic fermentation metabolites, and (3) the gut microbiome's role in the partitioning of tryptophan in its metabolic pathways. Tryptophan's main metabolic pathways include the indolic and the kynurenine pathways, which lead, respectively, to the formation of indoxyl sulfate and kynurenine, both contributing to uremic toxicity. Using a rat model of CKD, we evaluated whether fecal concentrations of microbial compounds, on which most studies are based, reflect the colonic concentrations in contact with the gut mucosa. Thus, we quantified the concentration and content of amino acids, indole, p-cresol, and also short-chain fatty acids, in different colon sections. We demonstrated that CKD promotes increased proteolytic fermentation and an augmented tryptophan partitioning into both the indolic and kynurenine pathways. Depletion of the indolic pathway obtained upon antibiotic treatment leads to a further enhancement of the kynurenine pathway.