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.
METHODS: Methods: Diet-induced obese male rats underwent RYGB (n¼8) or sham (n¼7) surgery with pre-and post-operative urine and stool collections at specified time-points. At 8 weeks post-surgery, all animals were placed on high-calcium diet (2.4%) for 2 weeks and then returned to normal calcium diet (0.6%) for 2 weeks. Rats were then orally gavaged with an actively growing, 24-hour pure culture of a wild, rat-colonizing strain of O.f. (35 mg of wet weight) and followed for 7 weeks. Alterations in intestinal microbiota were analyzed using 16S rRNA Illumina paired-end sequencing followed by UniFrac principal component analysis and linear discriminant analysis coupled with effect sized (LEfSe) measurements.RESULTS: Results: Gut microbial community structure was significantly different in RYGB animals compared to sham controls. Manipulation in dietary calcium had minimal effects on the gut microbiome structure. Oral gavage with O.f. induced a modest change in the overall microbial community structure in RYGB animals but not in sham animals. Interestingly, O.f. treatment increased the abundance of Bifidobacterium and Bacteroidales in RYGB animals, and reduced their urinary oxalate levels by 75%. The abundance of these species was not increased in sham animals.CONCLUSIONS: Conclusions: The RYGB procedure significantly altered the gut microbiome compared to controls. O.f. colonization but not dietary calcium manipulations in RYGB animals induced a modest change in the composition and structure of the intestinal microbiome. In contrast, the intestinal microbiota of sham animals was stable upon O.f. challenge. These data suggest that O.f. may serve as a keystone species in altering the intestinal microbial community in RYGB animals and warrant further studies in human RYGB patients.
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