Blood Microbiome Profile in CKD : A Pilot Study

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

30962186

DOI Digital object identifier for electronic documents.

10.2215/CJN.12161018

URI

Authors

Shah NB, Allegretti AS, Nigwekar SU, Kalim S, Zhao S, Lelouvier B, Servant F, Serena G, Thadhani RI, Raj DS, Fasano A

Journal

Clinical journal of the American Society of Nephrology : CJASN

Year

2019

Keywords:

Blood microbiome, Cross-Sectional Studies, DNA, Bacterial, Ribosomal, Dysbiosis, Endotoxemia, Enterobacteriaceae, Metagenomics, Microbiota, Permeability, Pilot Projects, Polymerase Chain Reaction, Proteobacteria, Pseudomonadaceae, Renal Insufficiency, Chronic, Sequence Analysis, chronic kidney disease, glomerular filtration rate

BACKGROUND AND OBJECTIVES: The association between gut dysbiosis, high intestinal permeability, and endotoxemia-mediated inflammation is well established in CKD. However, changes in the circulating microbiome in patients with CKD have not been studied. In this pilot study, we compare the blood microbiome profile between patients with CKD and healthy controls using 16S ribosomal DNA sequencing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Blood bacterial DNA was studied in buffy coat samples quantitatively by 16S PCR and qualitatively by 16S targeted metagenomic sequencing using a molecular pipeline specifically optimized for blood samples in a cross-sectional study comparing 20 nondiabetic patients with CKD and 20 healthy controls. RESULTS: There were 22 operational taxonomic units significantly different between the two groups. 16S metagenomic sequencing revealed a significant reduction in α diversity (Chao1 index) in the CKD group compared with healthy controls (127±18 versus 145±31; P=0.04). Proteobacteria phylum, Gammaproteobacteria class, and Enterobacteriaceae and Pseudomonadaceae families were more abundant in the CKD group compared with healthy controls. Median 16S ribosomal DNA levels did not significantly differ between CKD and healthy groups (117 versus 122 copies/ng DNA; P=0.38). GFR correlated inversely with the proportion of Proteobacteria (r=-0.54; P≤0.01). CONCLUSIONS: Our pilot study demonstrates qualitative differences in the circulating microbiome profile with lower α diversity and significant taxonomic variations in the blood microbiome in patients with CKD compared with healthy controls.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

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: Blood Portion of blood,Vertebrate blood,Whole blood,Blood

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

Group 0 name Corresponds to the control (unexposed) group for case-control studies: controls
Group 1 name Corresponds to the case (exposed) group for case-control studies: CKD
Group 0 sample size Number of subjects in the control (unexposed) group: 20
Group 1 sample size Number of subjects in the case (exposed) group: 20
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): current use

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: LEfSe

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
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, leukocyte, hypertension, hyperlipidemia, immunosuppressant use measurement

Alpha Diversity

Chao1 Abundance-based estimator of species richness: decreased

Signature 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): Lwaldron, WikiWorks

Source: Figure 3 and Table 2

Description: Linear discriminant analysis Effect Size (LEfSe) showing microbiome differences between groups at various taxonomic levels.

Abundance in Group 1: increased abundance in CKD

NCBI	Quality Control	Links
Acetobacteraceae
Acinetobacter
Azotobacter group
Bacillus
Chitinophagaceae
Enterobacterales
Enterobacteriaceae
Gammaproteobacteria
Hyphomicrobiaceae
Hyphomicrobium
Legionella
Legionellaceae
Legionellales
Lysobacter
Peptostreptococcaceae
Pseudomonadota
Pseudarcicella
Pseudomonas
Sediminibacterium
Serratia
Yersinia
Yersinia intermedia
Rhodospirillales

Revision editor(s): Lwaldron, WikiWorks

Signature 2

Edit History Delete

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Your review change was submitted

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): Lwaldron, Fatima, WikiWorks

Source: Figure 3 and Table 2

Description: Linear discriminant analysis Effect Size (LEfSe) showing microbiome differences between groups at various taxonomic levels.

Abundance in Group 1: decreased abundance in CKD

NCBI	Quality Control	Links
Acidimicrobiaceae
Acidimicrobiales
Terriglobia
Aurantimicrobium
Bryobacter
Bryobacterales
Corynebacterium
Desulfobulbaceae
Galloisiana yuasai
Lachnospiraceae
Microscillaceae
Ohtaekwangia
Paracoccus
Sphingomonas
Stenotrophomonas
Tyzzerella

Revision editor(s): Lwaldron, Fatima, WikiWorks