Category: Basic Science: Stones
Introduction & Objective :
Urinary stone disease (USD) is intimately tied to the microbiome. Diverse bacteria in the gut normally degrade oxalate, but individuals that form calcium oxalate stones have lower colonization rates of oxalate-degrading bacteria. Additionally, struvite stones can result from urinary tract infections. However, recent studies have shown that microbial oxalate metabolism is a function provided by a diverse network of bacteria and that the urinary tract also hosts its own diverse microbiome. Thus, the objectives of the current study were to take a multi-specimen, multi-omics approach to understand how dysbiosis affects the risk of developing USD.
We recruited 43 individuals with no history of USD along with 24 USD patients in this comparative study. Stool and urine was collected from each individual and DNA was extracted either directly from each sample, or after bacteria were cultured from urine with standard clinical procedures. The DNA was submitted to high throughput sequencing of the 16S rRNA gene to generate microbial inventories from each sample. Additionally, urine samples from both groups were subjected to untargeted metabolomics. Resulting data were compared across groups of patients, specimen types, and between samples where DNA was extracted directly and those that were first cultured. Sequencing and metabolomic data were integrated to determine the nature and location of dysbiosis associated with USD.
Antibiotic use was significantly higher in patients with USD. The microbiome of the urinary tract, but not the gastrointestinal tract, was significantly different by USD-status. The difference in the urinary tract microbiome extended to antibiotic use, sex, and both a personal and family history of USD. Integration of the metabolomic and sequencing data revealed that the urinary tract microbiome had a greater association with the urinary metabolome than did the gastrointestinal microbiome, with healthy individuals harboring a more extensive functional microbial network in the urinary tract than patients with USD. Finally, our results revealed that conventional culturing techniques to explore the bacteria in urine samples biases results towards Firmicutes bacteria.
Results of our study indicate that USD is associated with a loss of function dysbiosis, primarily of the urinary tract. This dysbiosis may be driven by antibiotic use, and is persistent with effects apparent across generations. These results are contrary to the conventional wisdom that infections of the urinary tract or loss of specific gut bacteria drive stone formation.
Cleveland Clinic Foundation
My name is Aaron W. Miller, Ph.D., a project scientist at Cleveland Clinic Foundation. My research focuses on interactions between the microbiome and urinary stone disease specifically for the development of a suite of bacteriotherapies designed to prevent urinary stone disease.