Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study

Study information

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study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

27640125

DOI Digital object identifier for electronic documents.

10.1186/s40168-016-0195-9

URI

Authors

Crespo-Salgado J, Vehaskari VM, Stewart T, Ferris M, Zhang Q, Wang G, Blanchard EE, Taylor CM, Kallash M, Greenbaum LA, Aviles DH

Journal

Microbiome

Year

2016

Keywords:

Children, End-stage renal disease, Inflammation, Intestinal microbiota, Pyrosequencing, Uremic toxins

BACKGROUND: End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins. METHODS: Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls. Stool bacterial composition was assessed by pyrosequencing analysis of 16S rRNA genes. Serum levels of C-reactive protein (CRP), D-lactate, p-cresyl sulfate and indoxyl sulfate were measured. RESULTS: Compared to controls, the relative abundance of Firmicutes (P = 0.0228) and Actinobacteria (P = 0.0040) was decreased in PD patients. The relative abundance of Bacteroidetes was increased in HD patients (P = 0.0462). Compared to HD patients the relative abundance of Proteobacteria (P = 0.0233) was increased in PD patients. At the family level, Enterobacteriaceae was significantly increased in PD patients (P = 0.0020) compared to controls; whereas, Bifidobacteria showed a significant decrease in PD and transplant patients (P = 0.0020) compared to control. Alpha diversity was decreased in PD patients and kidney transplant using both phylogenetic and non-phylogenetic diversity measures (P = 0.0031 and 0.0003, respectively), while beta diversity showed significant separation (R statistic = 0.2656, P = 0.010) between PD patients and controls. ESRD patients had increased serum levels of p-cresyl sulfate and indoxyl sulfate (P < 0.0001 and P < 0.0001, respectively). The data suggests that no significant correlation exists between the alpha diversity of the intestinal microbiota and CRP, D-lactate, or uremic toxins. Oral iron supplementation results in expansion of the phylum Proteobacteria. CONCLUSIONS: Children with ESRD have altered intestinal microbiota and increased bacterially derived serum uremic toxins.

Experiment 1

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Curated date: 2021/01/10

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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: chronic kidney disease , stage 5 chronic kidney disease chronic kidney disease,chronic kidney failure,Chronic Kidney Insufficiencies,Chronic Kidney Insufficiency,chronic renal disease,Chronic Renal Failure,chronic renal failure syndrome,Chronic Renal Insufficiencies,chronic renal insufficiency,CKD,CKD - chronic kidney disease,Disease, End-Stage Kidney,Disease, End-Stage Renal,END STAGE KIDNEY DIS,End Stage Kidney Disease,END STAGE RENAL DIS,End Stage Renal Disease,End-Stage Kidney Disease,End-Stage Renal Disease,End-Stage Renal Failure,ESRD,kidney disease, chronic,Kidney Disease, End-Stage,Kidney Failure, Chronic,Kidney Insufficiencies, Chronic,Kidney Insufficiency, Chronic,RENAL DIS END STAGE,Renal Disease, End Stage,Renal Disease, End-Stage,renal failure - chronic,Renal Failure, Chronic,Renal Failure, End Stage,Renal Failure, End-Stage,Renal Insufficiencies, Chronic,Renal Insufficiency, Chronic,chronic renal failure,End stage renal disease,End stage renal failure,end-stage renal disease,End-stage renal failure,end stage renal disease,stage 5 chronic kidney disease

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: peritoneal dialysis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: 4 groups of pediatric patients (age 2-18), hemodialysis, peritoneal dialysis, kidney transplant, healthy controls
Group 0 sample size Number of subjects in the control (unexposed) group: 13
Group 1 sample size Number of subjects in the case (exposed) group: 8
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

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

Statistical Analysis

Statistical test: Kruskall-Wallis

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

Alpha Diversity

Chao1 Abundance-based estimator of species richness: decreased
Richness Number of species: decreased

Signature 1

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Source: Figure 2

Description: Relative abundance of the four dominant phyla of the intestinal microbiota

Abundance in Group 1: decreased abundance in peritoneal dialysis

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Bacillota
Actinomycetota

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Signature 2

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Source: Figure 2

Description: Relative abundance of the four dominant phyla of the intestinal microbiota

Abundance in Group 1: increased abundance in peritoneal dialysis

NCBI	Quality Control	Links
Pseudomonadota

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Experiment 2

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Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies: hemodialysis

Lab analysis

Statistical Analysis

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

Alpha Diversity

Chao1 Abundance-based estimator of species richness: unchanged
Richness Number of species: unchanged

Signature 1

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Source: Figure 2

Description: Relative abundance of the four dominant phyla of the intestinal microbiota

Abundance in Group 1: increased abundance in hemodialysis

NCBI	Quality Control	Links
Bacteroidota

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Experiment 3

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: peritoneal dialysis
Group 0 sample size Number of subjects in the control (unexposed) group: 8