Login to Access Video or Poster Abstract: MP19-01
Sources of Funding: NIH R21 DK108097-01A1

Introduction

Kidney stone disease (KSD) is a common urological disorder in the United States with a prevalence of 11% and 7% in men and women, respectively. Several factors are known to increase an individual's risk for KSD including obesity, diabetes, metabolic syndrome and poor nutrition; interestingly, each of these factors has a well-documented association with the human gut microbiome both in terms of taxonomic composition and metabolic capacity. In this study we applied high-resolution gut microbiome analysis to identify significant shifts in bacterial species composition and associated functional gene content between kidney stone formers and non-stone forming controls.

Methods

16S rRNA amplicon sequences generated by the Illumina MiSeq platform were filtered for quality and contaminants, and subsequently analyzed using the Resphera Insight algorithm for high-resolution taxonomic assignment. Species abundances were then assessed for significant enrichment or depletion in stone formers relative to controls utilizing the negative binomial test followed by False Discovery Rate p-value adjustment. Functional gene content was also assessed with PICRUSt.

Results

A total of 23 patients with KSD and six non-stone-forming controls maintained an average of 3,893 sequences per sample. Species-level profiling with Resphera Insight revealed significantly different levels of several species including 90% reductions of Prevotella buccalis and Prevotella corporis in the KSD group (adj.P<0.01). We also observe relative increases of Bacteroides and Clostridia species in KSD patients including a 27-fold increase in Bacteroides acidifaciens (adj.P=1e-6), and a 40-fold increase in Clostridium ramosum (adj.P=6e-12). Functional characterization identified KEGG pathways enriched in KSD relative to controls, including primary and secondary bile acid synthesis (P=0.001), a 3-fold increase in steroid hormone synthesis (P=0.007), as well as fructose metabolism, galactose metabolism and glycosaminoglycan degradation.

Conclusions

KSD patients maintain significantly higher levels of specific Bacteroides and Clostridia species and significantly lower Prevotella species as compared to controls. Enrichments in multiple categories of metabolism were also identified. The gut microbiome may interact with kidney stone formation and identification of pathways and species level bacteria may allow for directed studies that will in the future build upon these findings.

Funding

NIH R21 DK108097-01A1