Diet quality, protein-bound uraemic toxins and gastrointestinal microbiome in chronic kidney disease

Abstract

Background and Aims Individuals with chronic kidney disease (CKD) have significantly increased risk of cardiovascular mortality which is only partially explained by Framingham risk factors. There is a growing body of evidence linking the gut-derived uraemic toxins indoxyl sulphate (IS) and p-cresyl sulphate (PCS) with accelerated kidney disease progression and cardiovascular burden in CKD. Whilst the effect of specific nutrients on uraemic toxin generation has been explored, few studies have characterised the impact of diet quality on the gastrointestinal microbiome in the CKD population. This study aims to explore the associations between dietary quality, protein-bound uraemic toxins and gastrointestinal microbiome in adults with CKD.

Method This was a baseline cross-sectional study of adults with stage 3 to 4 CKD who were enrolled in a randomised controlled trial of prebiotic and probiotic supplementation. Habitual dietary intake was measured using a 7-day diet history method by a specialist Dietitian. Diet quality was assessed using food group analysis; protein intake, fibre intake, dietary protein:fibre ratio and adherence to plant-based diet index (PDI) (overall PDI, healthy PDI, unhealthy PDI). Serum uraemic toxins (free and total; IS and PCS) were determined by ultra-performance liquid chromatography. Metagenomic sequencing was used to determine gastrointestinal microbiota richness, diversity, composition and functional capacity.

Results There were 68 CKD patients [66% male, median age 70 (IQR 58-75) years] with a mean estimated glomerular filtration rate of 34 ± 11 mL/min/1.73m2. Greater adherence to a hPDI was associated with lower levels of free PCS [-0.021 µmol/L (95% CI -0.042 to -0.001)], while a higher intake of dietary fibre intake was associated with lower levels of free IS [-0.022 µmol/L (95% CI -0.043 to -0.001)]. Compositionally, the gastrointestinal microbiota of this cohort was dominated by members of the phyla Firmicutes and Bacteroidetes. Supervised analysis at the species level demonstrated that 21% of variance in gastrointestinal microbial composition could be attributed to protein:fibre ratio (F=1.27, p=0.04). Further, a higher protein:fibre ratio was associated with an increased relative abundance of unclassified members of order Oscillospirales. Subdoligranulum formicile was correlated with dietary intake of vegetables and wholegrains while an unclassified Prevotella species was correlated with food items considered discretionary including sweet drinks, sweet desserts, animal fats and potatoes.

Conclusion The study suggests that habitual diets that are higher in fibre and plant-based foods may positively influence uraemic toxin levels and gut microbiota diversity and composition in adults with CKD. These findings provide rationale for well-designed dietary intervention studies targeting the production of uraemic toxins and exploring the impact on gut microbiome in the CKD population.