Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone Disease

Study information

Reviewed Marked as Reviewed by Atrayees on 2023-6-8

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32381601

DOI Digital object identifier for electronic documents.

10.1681/ASN.2019101131

URI

https://jasn.asnjournals.org/content/31/6/1358.abstract

Authors

Denburg MR, Koepsell K, Lee JJ, Gerber J, Bittinger K, Tasian GE

Journal

Journal of the American Society of Nephrology : JASN

Year

2020

Keywords:

intestine, kidney stones, metabolism, pediatric nephrology

BACKGROUND: The relationship between the composition and function of gut microbial communities and early-onset calcium oxalate kidney stone disease is unknown. METHODS: We conducted a case-control study of 88 individuals aged 4-18 years, which included 44 individuals with kidney stones containing ≥50% calcium oxalate and 44 controls matched for age, sex, and race. Shotgun metagenomic sequencing and untargeted metabolomics were performed on stool samples. RESULTS: Participants who were kidney stone formers had a significantly less diverse gut microbiome compared with controls. Among bacterial taxa with a prevalence >0.1%, 31 taxa were less abundant among individuals with nephrolithiasis. These included seven taxa that produce butyrate and three taxa that degrade oxalate. The lower abundance of these bacteria was reflected in decreased abundance of the gene encoding butyryl-coA dehydrogenase (P=0.02). The relative abundance of these bacteria was correlated with the levels of 18 fecal metabolites, and levels of these metabolites differed in individuals with kidney stones compared with controls. The oxalate-degrading bacterial taxa identified as decreased in those who were kidney stone formers were components of a larger abundance correlation network that included Eggerthella lenta and several Lactobacillus species. The microbial (α) diversity was associated with age of stone onset, first decreasing and then increasing with age. For the individuals who were stone formers, we found the lowest α diversity among individuals who first formed stones at age 9-14 years, whereas controls displayed no age-related differences in diversity. CONCLUSIONS: Loss of gut bacteria, particularly loss of those that produce butyrate and degrade oxalate, associates with perturbations of the metabolome that may be upstream determinants of early-onset calcium oxalate kidney stone disease.

Experiment 1

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Reviewed Marked as Reviewed by Atrayees on 2023-6-8

Curated date: 2023/03/23

Curator: Blessing Kaz

Revision editor(s): Claregrieve1, Atrayees, Aiyshaaaa, Blessing Kaz

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: 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,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Nephrolithiasis 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,Nephrolithiasis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Patients with kidney stones

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: The patients suffering from Kidney Stones (nephrolithiasis) are individuals with incident and recurrent kidney stones consisting of 100% calcium (of which at least 50% was calcium oxalate) that spontaneously passed or were removed surgically within the prior 3 years.

Group 0 sample size Number of subjects in the control (unexposed) group: 44

Group 1 sample size Number of subjects in the case (exposed) group: 44

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: T-Test

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Matched on Factors on which subjects have been matched on in a case-control study: age, race, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Richness Number of species: decreased

Signature 1

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Curated date: 2023/03/26

Curator: Blessing Kaz

Revision editor(s): Blessing Kaz, Aiyshaaaa, Atrayees

Source: figure 1

Description: The relative abundance of bacterial taxa among participants with kidney stone disease.

Abundance in Group 1: decreased abundance in Patients with kidney stones

NCBI	Quality Control	Links
Roseburia hominis
Faecalitalea cylindroides
Clostridioides difficile
unclassified Bacillota
unclassified Eubacteriales
Oscillibacter valericigenes
unclassified Lachnospiraceae
Ruminococcus champanellensis
Enterococcus faecium
Ethanoligenens harbinense
Eubacterium limosum
Ruminococcus albus
Butyrivibrio proteoclasticus
Streptococcus suis
Treponema succinifaciens
Mageeibacillus indolicus
Nitratidesulfovibrio vulgaris
Streptococcus pyogenes
Clostridium botulinum
Desulfovibrio desulfuricans
Slackia heliotrinireducens
Campylobacter jejuni
Enterococcus faecalis
Campylobacter coli
Clostridium perfringens
Bifidobacterium animalis

Revision editor(s): Blessing Kaz, Aiyshaaaa, Atrayees