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

Abstract

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.

Oral Antibiotic Exposure and Kidney Stone Disease

“…34 These prior studies, however, identified differences in the abundance of other bacteria such as Eubacterium and reported that patients with kidney stones had an lower overall diversity of the gut microbiome. 3,4 This lower diversity is consistent with the loss of microbiota diversity reported in other diseases, such as asthma. 35 It is likely that multiple organisms would mediate the association between antibiotics and nephrolithiasis because intestinal microbes exist as a community of organisms, with the metabolic functions of one species affecting growth of others.…”

“…Recent studies reported differences in the composition of the intestinal microbiome between patients with and without nephrolithiasis. 3,4 Additionally, multidrug resistant nonurease-producing bacteria have been isolated from calcium-based kidney stones extracted from patients without urinary tract infection (UTI), suggesting a role for selective pressure on the urinary microbiome in kidney stone formation. 5 However, despite the well established effect that antibiotics have on the microbiome, it remains unclear whether antibiotics are a risk factor for nephrolithiasis.…”

The role of the microbiome in kidney stone formation

“…A recent study has identified distinct differences in the gut microbiome of kidney stone patients compared to patients without stones [3]. Fecal and urine samples collected from both groups of patients revealed 178 genera, of which the five most abundant enterotypes, or distinct bacterial communities, within each group made up greater than 50% of the bacterial abundance identified.…”

Overexpression of miR‑30c‑5p reduces cellular cytotoxicity and inhibits the formation of kidney stones through ATG5

“…Kidney stone formation is a common disease with a high morbidity (1). Kidney stones can lead to the development of severe diseases such as hydronephrosis, renal function impairment or insufficiency if active treatment is not undertaken.…”