A Metagenomic Approach Does Not Elucidate Uremic Toxin Levels in Hemodialysis Patients.

Abstract

Blood levels of uremic molecules generated through gut microbial metabolism are associated with disease risk, reduced quality of life, and mortality in patients with renal insufficiency. Modulation of the microbiome may offer therapeutic potential. Objective: This study aimed to elucidate the relationships between fecal microbiome and serum levels of targeted uremic molecules in adults undergoing hemodialysis and, secondarily, the role of relative macronutrient substrate availability. Methods: Fecal microbiota was profiled by whole metagenome sequencing, serum p cresyl sulfate (CS), indoxyl sulfate (IS), phenylacetylglutamine (PAG), and trimethylamine N oxide (TMAO) were quantified by liquid chromatography tandem mass spectrometry (LC MS/MS), and dietary intake was assessed by three multipass-method 24-hr recalls. Results: Differences in gut microbiome associated with serum uremic toxin levels were not detected. Instead, the relative substrate availability for the microbiota, using dietary protein-to-fiber ratio, was significantly associated with uremia. Serum levels of IS (multivariate linear model, p=0.042) and TMAO (p=0.032) were positively associated with dietary protein-to-fiber ratio, but not CS (p=0.096) and PAG (p=0.44). Conclusion: The lack of association of fecal microbiome with serum uremic toxins suggests that hemodialysis patients possess sufficient microbial enzymatic capacity for the synthesis of these molecules and that, instead, microbially available substrate, protein vs. fiber, may be the primary driver of production.