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

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study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Denburg MR, Koepsell K, Lee JJ, Gerber J, Bittinger K, Tasian GE
Journal
Journal of the American Society of Nephrology : JASN
Year
2020
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


Needs review

Curated date: 2023/03/23

Curator: Blessing Kaz

Revision editor(s): Blessing Kaz, Claregrieve1

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
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
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
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
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).
centered log-ratio
Statistical test
Mann-Whitney (Wilcoxon)
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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2.0
Matched on Factors on which subjects have been matched on in a case-control study
age, race, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, race, sex

Alpha Diversity

Pielou Quantifies how equal the community is numerically
decreased
Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased
Richness Number of species
decreased

Signature 1

incomplete

Curated date: 2023/03/26

Curator: Blessing Kaz

Revision editor(s): Blessing Kaz, Aiyshaaaa

Source: figure 4

Description: taxonomic abundance of the gut microbiome in individuals who formed kidney stones at different ages, as measured by species richness and Shannon diversity

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

NCBI Links
Acidobacteriota
Bifidobacterium animalis
Blautia obeum
Cyanobacteriota
Eggerthella lenta
Enterococcus faecalis
Enterococcus faecium
Lactobacillus acidophilus
Lactobacillus gasseri
Lactobacillus johnsonii
Leuconostoc mesenteroides
Ligilactobacillus salivarius
Oxalobacter formigenes
Planctomycetales
Ruminococcus obeum CAG:39
Verrucomicrobiota

Revision editor(s): Blessing Kaz, Aiyshaaaa

Signature 2

incomplete

Curated date: 2023/03/26

Curator: Blessing Kaz

Revision editor(s): Blessing Kaz, Aiyshaaaa

Source: figure 2c

Description: The differential abundance of bacterial taxa of species at genus, class, phylum, order and family level in both the groups between calcium oxalate kidney stone formers and healthy controls.

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

NCBI Links
Bilophila
Campylobacter coli
Campylobacter jejuni
Escherichia coli
Prevotella copri

Revision editor(s): Blessing Kaz, Aiyshaaaa