Defining Dysbiosis in Patients with Urolithiasis

Anna Zampini,Aaron W Miller,Andrew H Nguyen,Manoj Monga,Emily Rose

doi:10.1038/s41598-019-41977-6

Anna Zampini, Aaron W Miller + Show 3 more

Open Access

https://doi.org/10.1038/s41598-019-41977-6

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Abstract

The prevalence of urinary stone disease (USD) is rapidly rising. However, the factors driving this increase are unknown. Recent microbiome studies suggest that dysbiosis may in part contribute to the increasing prevalence. The objective of the current study was to determine the nature and location of dysbiosis associated with USD. We conducted microbiome analysis from the gastrointestinal and urinary tracts, along with a metabolomic analysis of the urinary metabolome, from subjects with an active episode of USD or no history of the disease. Higher rates of antibiotic use among USD patients along with integrated microbiome and metabolomic results support the hypothesis that USD is associated with an antibiotic-driven shift in the microbiome from one that protects against USD to one that promotes the disease. Specifically, our study implicates urinary tract Lactobacillus and Enterobacteriaceae in protective and pathogenic roles for USD, respectively, which conventional, culture-based methods of bacterial analysis from urine and kidney stones would not necessarily detect. Results suggest that antibiotics produce a long-term shift in the microbiome that may increase the risk for USD, with the urinary tract microbiome holding more relevance for USD than the gut microbiome.

Highlights

The prevalence of urinary stone disease (USD) is approximately 8.8%, representing a four-fold increase from fifty years ago[1]
If antibiotics can alleviate disease symptoms or microbial transplants can cause disease symptoms, gain of function dysbiosis contributes to the disease process
Several studies have found that patients with USD are colonized by O. formigenes www.nature.com/scientificreports at lower rates than healthy individuals[62,63,64,65,66,67,68,69]; that individuals colonized by O. formigenes have lower urinary oxalate[62,66,67,68,70,71,72,73]; and that O. formigenes is sensitive to several classes of antibiotics[62,69,74,75]

Summary

Introduction

The prevalence of urinary stone disease (USD) is approximately 8.8%, representing a four-fold increase from fifty years ago[1]. A combination of loss and gain of function dysbiosis may contribute to or be required for some disease processes Such is the case with recurrent Clostridium difficile infection, in which repeated antibiotic use leads to the depletion of the commensal microbiota, which allows for the proliferation of pathogenic C. difficile[28]. If antibiotics can alleviate disease symptoms or microbial transplants can cause disease symptoms, gain of function dysbiosis contributes to the disease process. If antibiotics can cause disease symptoms or microbial transplants can alleviate disease symptoms, loss of function dysbiosis contributes to the disease Bacteria both in the urinary and gastrointestinal tracts have been linked to USD through both gain and loss of function mechanisms. If loss of function dysbiosis contributes to calcium oxalate stone formation, bacteria other than oxalate-degrading bacteria must be involved

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