Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition

Kachroo, Naveen; Lange, Dirk; Penniston, Kristina L.; Stern, Joshua M.; Tasian, Gregory E.; Bajic, Petar; Wolfe, Alan J.; Suryavanshi, Mangesh V.; Ticinesi, Andrea; Meschi, Tiziana; Monga, Manoj; Miller, Aaron W.

doi:10.1128/mbio.02007-21

Cited by 31 publications

(25 citation statements)

References 31 publications

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“…Consistent with their reports, we found that E. coli also accounted for a greater proportion of the microbiomes in nephrolithiasis patients than in healthy individuals. Additionally, previous studies have determined that the genus Staphylococcus was overrepresented, while Lactobacillus was less abundant in nephrolithiasis patients than in healthy controls ( Zampini et al., 2019 ; Liu et al., 2020a ; Kachroo et al., 2021 ); again, our findings support these reports. It has been shown that Staphylococcus promotes the formation of kidney stones by producing the enzyme urease, which increases pH, while Lactobacilli exerts an inhibitory action by degrading oxalate ( Lewanika et al., 2007 ; Torzewska et al., 2019 ).…”

Section: Discussionsupporting

confidence: 91%

Urinary Microbial and Metabolomic Profiles in Kidney Stone Disease

Guo

Lin

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundKidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone formation remains elusive. We performed a multi-omic study investigating urinary microbial compositions and metabolic alterations during nephrolithiasis.MethodUrine samples from healthy and individuals with nephrolithiasis were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectroscopy. Microbiome and metabolome profiles were analyzed individually and combined to construct interactome networks by bioinformatic analysis.ResultsDistinct urinary microbiome profiles were determined in nephrolithiasis patients compared with controls. Thirty-nine differentially abundant taxa between controls and nephrolithiasis patients were identified, and Streptococcus showed the most significant enrichment in nephrolithiasis patients. We also observed significantly different microbial compositions between female and male nephrolithiasis patients. The metabolomic analysis identified 112 metabolites that were differentially expressed. Two significantly enriched metabolic pathways, including biosynthesis of unsaturated fatty acids and tryptophan metabolism, were also identified in nephrolithiasis patients. Four potentially diagnostic metabolites were also identified, including trans-3-hydroxycotinine, pyroglutamic acid, O-desmethylnaproxen, and FAHFA (16:0/18:2), and could function as biomarkers for the early diagnosis of nephrolithiasis. We also identified three metabolites that contributed to kidney stone size. Finally, our integrative analysis of the urinary tract microbiome and metabolome identified distinctly different network characteristics between the two groups.ConclusionsOur study has characterized important profiles and correlations among urinary tract microbiomes and metabolomes in nephrolithiasis patients for the first time. These results shed new light on the pathogenesis of nephrolithiasis and could provide early clinical biomarkers for diagnosing the disease.

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Section: Discussionsupporting

confidence: 91%

Urinary Microbial and Metabolomic Profiles in Kidney Stone Disease

Guo

Lin

et al. 2022

Front. Cell. Infect. Microbiol.

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“…More recently, distinct shifts in the diversity and composition of the urinary and urogenital microbiomes were observed in human urolith formers 9,10,18 . In fact, a comprehensive analysis of the gut and urogenital microbiomes determined that the urogenital microbiome exhibited more pronounced alterations by urolith status than did the gut microbiome 9 .…”

Section: Introductionmentioning

confidence: 99%

“…17 More recently, distinct shifts in the diversity and composition of the urinary and urogenital microbiomes were observed in human urolith formers. 9,10,18 In fact, a comprehensive analysis of the gut and urogenital microbiomes determined that the urogenital microbiome exhibited more pronounced alterations by urolith status than did the gut microbiome. 9 Microbial communities also recently have been identified in the urine of healthy dogs, [19][20][21] but the role of these microbes in CaOx formation in dogs is unknown.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the urogenital microbiome in Miniature Schnauzers with and without calcium oxalate urolithiasis

Coffey

Gómez

Burton

et al. 2022

Veterinary Internal Medicne

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Background: Calcium oxalate (CaOx) uroliths are common in dogs. Humans with CaOx urolithiasis exhibit alterations of the urinary and urogenital microbiomes that might mediate urolith formation. Detection of urogenital microbes associated with CaOx in dogs could inform disease pathophysiology. Objective: To identify compositional differences in the urogenital microbiome of Miniature Schnauzers with and without CaOx uroliths. Animals: Nineteen midstream, voided urine samples from Miniature Schnauzers with (n = 9) and without (n = 10) a history of CaOx urolithiasis. Methods: Analytical cross-sectional study. Microbial DNA was extracted from previously frozen urine samples and sequenced for the bacterial 16S rRNA V3-V4 hypervariable regions. Diversity and composition of microbial populations were compared between urolith formers and controls. Results: Alpha and beta diversity measures were similar between groups. Five individual bacterial taxa differed in abundance (indicator values >0.5 and P < .05):Acinetobacter, 2 Geobacillus variants, and Hydrogenophaga were overrepresented in the urine of urolith formers, and Sphingopyxis was overrepresented in controls. Two distinct subtypes of urine microbial composition were observed based on beta diversity measures, independent of urolith status, and other clinical variables.Conclusions and Clinical Importance: Although we did not detect a difference in the overall urogenital microbial composition between groups, observed differences in individual bacterial taxa might be clinically relevant. For example, Acinetobacter was overrepresented in urolith formers and is associated with CaOx urolithiasis in humans. Two unique clusters of the microbiome were identified, independent of urolith status, which may represent distinct urotypes present in Miniature Schnauzers.

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“…There are many hypotheses but none are definitive. The incidence of urinary stones is related to age, gender, race, dietary habits, genetics, and metabolism ( Sayer, 2017 ; Taguchi et al., 2017 ; Jung et al., 2018 ; Kachroo et al., 2021 ). Urinary stones are also closely associated with microbial taxa ( Dornbier et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Identifying Two Novel Clusters in Calcium Oxalate Stones With Urinary Tract Infection Using 16S rDNA Sequencing

Shen

Zhu

Fan

et al. 2021

Front. Cell. Infect. Microbiol.

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Urinary stones and urinary tract infection (UTI) are the most common diseases in urology and they are characterized by high incidence and high recurrence rate in China. Previous studies have shown that urinary stones are closely associated with gut or urine microbiota. Calcium oxalate stones are the most common type of urinary stones. However, the profile of urinary tract microorganisms of calcium oxalate stones with UTI is not clear. In this research, we firstly found two novel clusters in patients with calcium oxalate stones (OA) that were associated with the WBC/HP (white blood cells per high-power field) level in urine. Two clusters in the OA group (OA1 and OA2) were distinguished by the key microbiota Firmicutes and Enterobacteriaceae. We found that Enterobacteriaceae enriched in OA1 cluster was positively correlated with several infection-related pathways and negatively correlated with a few antibiotics-related pathways. Meantime, some probiotics with higher abundance in OA2 cluster such as Bifidobacterium were positively correlated with antibiotics-related pathways, and some common pathogens with higher abundance in OA2 cluster such as Enterococcus were positively correlated with infection-related pathways. Therefore, we speculated that as a sub-type of OA disease, OA1 was caused by Enterobacteriaceae and the lack of probiotics compared with OA2 cluster. Moreover, we also sequenced urine samples of healthy individuals (CK), patients with UTI (I), patients with uric acid stones (UA), and patients with infection stones (IS). We identified the differentially abundant taxa among all groups. We hope the findings will be helpful for clinical treatment and diagnosis of urinary stones.

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Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition

Abstract: Studies focused on the microbiome broadly support the hypothesis that the microbiome influences the onset of chronic diseases such as urinary stone disease. However, it is unclear what environmental factors shape the microbiome in ways that increase the risk for chronic disease.

Cited by 31 publications

References 31 publications

Urinary Microbial and Metabolomic Profiles in Kidney Stone Disease

Urinary Microbial and Metabolomic Profiles in Kidney Stone Disease

Characterization of the urogenital microbiome in Miniature Schnauzers with and without calcium oxalate urolithiasis

Identifying Two Novel Clusters in Calcium Oxalate Stones With Urinary Tract Infection Using 16S rDNA Sequencing

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