Identification of Gut Microbiome Signatures Associated with the Kynurenine Pathway in Tryptophan Metabolism in Patients Undergoing Hemodialysis

This is the authors' abstract. We don't add key points for this paper.

Patients with chronic kidney disease (CKD) and hemodialysis (HD) often experience gut microbiota dysbiosis, which may influence tryptophan metabolism through the kynurenine pathway. We aimed to investigate the specific gut microbiota signatures associated with metabolites involved in the kynurenine pathway in HD patients. In this cross-sectional study, we analyzed serum metabolite concentrations and fecal shotgun metagenomic profiles from 85 patients receiving maintenance hemodialysis at Kaohsiung Medical University Hospital. Fecal samples were analyzed using shotgun metagenomic sequencing to characterize microbiome composition and functional pathways. We measured kynurenine pathway metabolites (kynurenine, kynurenic acid, nicotinuric acid, and trigonelline) by liquid chromatography tandem mass spectrometry and analyzed their associations with microbial species abundance and genomic metabolic modules (GMM). Several bacterial species displayed associations with kynurenine pathway metabolites. Ruminococcus gnavus and Eubacterium sp. CAG:180 demonstrated correlations with kynurenine and kynurenic acid levels, respectively; however, these associations did not persist after adjustment. Distinct levels of metabolites corresponded to distinct patterns of genomic metabolic modules. High kynurenine levels correlated with increased pathways for pectin and arginine degradation. Elevated nicotinuric acid levels were associated with enhanced pathways for anaerobic fatty acid beta-oxidation and propionate production. Trigonelline levels correlated with homocysteine metabolism and various amino acid degradation pathways. Specific microbial taxa and predicted functional modules were associated with circulating kynurenine- and niacin-related metabolites. These cross-sectional findings are hypothesis-generating and do not establish directionality, causality, or therapeutic efficacy. Interpretation is limited by the modest sample size and the absence of a non-hemodialysis control group.