Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers

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study design
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Stern JM, Moazami S, Qiu Y, Kurland I, Chen Z, Agalliu I, Burk R, Davies KP
The trillions of microbes that colonize our adult intestine are referred to as the gut microbiome (GMB). Functionally it behaves as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. While the relationship between the GMB and kidney stone disease (KSD) has not been investigated, dysbiosis of the GMB has been associated with diabetes, obesity and cardiovascular disease. In this pilot study we sought to identify unique changes in the GMB of kidney stone patients compared to patients without KSD. With an IRB-approved protocol we enrolled 29 patients into our pilot study. 23 patients were kidney stone formers and six were non-stone forming controls. Specimens were collected after a 6h fast and were flash frozen in dry ice and then stored at -80 °C. Microbiome: determination of bacterial abundance was by analysis of 16 s rRNA marker gene sequences using next generation sequencing. Sequencing of the GMB identified 178 bacterial genera. The five most abundant enterotypes within each group made up to greater than 50 % of the bacterial abundance identified. Bacteroides was 3.4 times more abundant in the KSD group as compared to control (34.9 vs 10.2 %; p = 0.001). Prevotella was 2.8 times more abundant in the control group as compared to the KSD group (34.7 vs 12.3 %; p = 0.005). In a multivariate analysis including age, gender, BMI, and DM, kidney stone disease remained an increased risk for high prevalence for Bacteroides (OR = 3.26, p = 0.033), whereas there was an inverse association with Prevotella (OR = 0.37, p = 0.043). There were no statistically significant differences in bacterial abundance levels for Bacteroides or Prevotella when comparing patients with and without DM, obesity (BMI >30), HTN or HLD. 11 kidney stone patients completed 24 h urine analysis at the time of this writing. Looking at the bacterial genuses with at least 4 % abundance in the kidney stone group, Eubacterium was inversely correlated with oxalate levels (r = -0.60, p < 0.06) and Escherichia trended to an inverse correlation with citrate (r = -0.56, p < 0.08). We also compared bacterial abundance between uric acid (UA) stone formers (n = 5) and non UA stone formers (n = 18) and found no significant difference between them. We identified two genus of bacteria in the GMB that had significant association with KSD. Interestingly, components of the 24-h urine appear to be correlated to bacterial abundance. These preliminary studies for the first time associate differences in the GMB with kidney stone formation. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in kidney stone disease.

Experiment 1

Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks


Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
nephrolithiasis , urolithiasis Calculi, Kidney,Calculi, Renal,calculus of kidney and ureter,Calculus, Kidney,Calculus, Renal,CAON,Kidney Calculi,Kidney Calculus,kidney stone,Kidney Stones,Kidney stones,kidney stones,nephrolithiasis,nephrolithiasis, calcium oxalate,Renal Calculi,Renal calculi,renal calculi,Renal Calculus,Renal stones,Stone - kidney/ureter,Stone, Kidney,Stones, Kidney,urolithiasis, calcium oxalate,calculus,urinary stones,urolithiasis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy control
Group 1 name Corresponds to the case (exposed) group for case-control studies
kidney stone patient
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
kidney stone
Group 0 sample size Number of subjects in the control (unexposed) group
Group 1 sample size Number of subjects in the case (exposed) group
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 weeks

Lab analysis

Sequencing type
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?