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Comparative functional analysis of the urinary tract microbiome for individuals with or without calcium oxalate calculi

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Abstract

Individuals with urinary stone disease (USD) exhibit dysbiosis in the urinary tract and the loss of Lactobacillus that promote urinary tract health. However, the microbial metabolic functions that differentiate individuals with USD from healthy individuals are unknown. The objective of the current study was to determine the microbial functions across prokaryotic, viral, fungal, and protozoan domains that are associated with calcium oxalate (CaOx) stone formers through comparative shotgun metagenomics of midstream, voided urine samples for a small number of patients (n = 5 CaOx stone formers, n = 5 healthy controls). Results revealed that CaOx stone formers had reduced levels of genes associated with oxalate metabolism, as well as transmembrane transport, proteolysis, and oxidation–reduction processes. From 17 draft genomes extracted from the data and > 42,000 full length reference genomes, genes enriched in the Control group mapped overwhelming to Lactobacillus crispatus and those associated with CaOx mapped to Pseudomonas aeruginosa and Burkholderia sp. The microbial functions that differentiated the clinical cohorts are associated with known mechanisms of stone formation. While the prokaryotes most differentiated the CaOx and Control groups, a diverse, trans-domain microbiome was apparent. While our sample numbers were small, results corroborate previous studies and suggest specific microbial metabolic pathways in the urinary tract that modulate stone formation. Future studies that target these metabolic pathways as well as the influence of viruses, fungi, and protozoa on urinary tract physiology is warranted.

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Data availability

Raw sequence reads and metadata are available at the Sequence Read Archive under BioProject # PRJNA718167. Constructed genomes are available under BioProject #PRJNA717274.

Abbreviations

USD:

Urinary stone disease

CaOx:

Calcium oxalate

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Funding

NK was supported in part by the Urology Care Foundation Research Scholar Award Program and Endourological Society/Raju Thomas M.D. Award. Funding was also provided by NIH/NIDDK Grant 1R01DK121689-01A1 to AM.

Author information

Authors and Affiliations

  1. Department of Urology, Henry Ford Health System, Detroit, MI, USA

    Naveen Kachroo

  2. Department of Urology, University of California San Diego, San Diego, CA, USA

    Manoj Monga

  3. Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Aaron W. Miller

  4. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

    Aaron W. Miller

Authors
  1. Naveen Kachroo
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  2. Manoj Monga
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  3. Aaron W. Miller
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Correspondence to Aaron W. Miller.

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The authors have no conflicts of interests to report.

Ethics approval

The questionnaire and methodology for this study was approved by the Institutional Review Board of Cleveland Clinic (IRB# 16-643).

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Supplementary Information

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Fig. S1 Within group variance in Bray-Curtis dissimilarity of the metagenome profile.

Fig. S2 Significantly different microbial genes mapped to >42,000 reference genomes.

Table S1 Number of taxa in the urinary tract that differentiated CaOx patients from controls.

240_2022_1314_MOESM4_ESM.xlsx

Table S2 Microbial genes significantly different between the CaOx and Controls. Listed are the log2 fold change, p value and adjusted p value, group enriched, which genome the genes mapped to either the de novo or reference genomes, and the complete Gene Ontology annotation of the genes.

Supplementary file5 (XLSX 12 kb)

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Kachroo, N., Monga, M. & Miller, A.W. Comparative functional analysis of the urinary tract microbiome for individuals with or without calcium oxalate calculi. Urolithiasis 50, 303–317 (2022). https://doi.org/10.1007/s00240-022-01314-5

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  • DOI: https://doi.org/10.1007/s00240-022-01314-5

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