Exploring the Relevance between Gut Microbiota-Metabolites Profile and Chronic Kidney Disease with Distinct Pathogenic Factor

Study information

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study design

case-control

Citation

PMID PubMed identifier for scientific articles.

36475922

DOI Digital object identifier for electronic documents.

10.1128/spectrum.02805-22

URI

Authors

Chen TH, Cheng CY, Huang CK, Ho YH, Lin JC

Journal

Microbiology spectrum

Year

2023

Keywords:

chronic kidney disease, diabetes mellitus, fecal metabolite, gut microbiota, hypertension

The intimate correlation of chronic kidney disease (CKD) with structural alteration in gut microbiota or metabolite profile has been documented in a growing body of studies. Nevertheless, a paucity of demonstrated knowledge regarding the impact and underlying mechanism of gut microbiota or metabolite on occurrence or progression of CKD is unclarified thus far. In this study, a liquid chromatography coupled-mass spectrometry and long-read sequencing were applied to identify gut metabolites and microbiome with statistically-discriminative abundance in diabetic CKD patients (n = 39), hypertensive CKD patients (n = 26), or CKD patients without comorbidity (n = 40) compared to those of healthy participants (n = 60). The association between CKD-related species and metabolite was evaluated by using zero-inflated negative binomial (ZINB) regression. The predictive utility of identified operational taxonomic units (OTUs), metabolite, or species-metabolite association toward the diagnosis of incident chronic kidney disease with distinct pathogenic factor was assessed using the random forest regression model and the receiver operating characteristic (ROC) curve. The results of statistical analyses indicated alterations in the relative abundances of 26 OTUs and 41 metabolites that were specifically relevant to each CKD-patient group. The random forest regression model with only species, metabolites, or its association differentially distinguished the hypertensive, diabetic CKD patients, or enrolled CKD patients without comorbidity from the healthy participants. IMPORTANCE Gut dysbiosis-altered metabolite association exhibits specific and convincing utility to differentiate CKD associated with distinct pathogenic factor. These results present the validity of pathogenesis-associated markers across healthy participants and high-risk population toward the early screening, prevention, diagnosis, or personalized treatment of CKD.

Experiment 1

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Curated date: 2024/03/16

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Subjects

Location of subjects: Taiwan

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: 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 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: Chronic Kidney Disease

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Chronic kidney disease patients

Group 0 sample size Number of subjects in the control (unexposed) group: 60

Group 1 sample size Number of subjects in the case (exposed) group: 105

Lab analysis

Sequencing type: 16S

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: Nanopore

Statistical Analysis

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

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)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3

Alpha Diversity

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

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Signature 1

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Curated date: 2024/03/21

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Source: Figure 3

Description: Classification of operational taxonomy unit (OTU) with long-read sequencing in healthy participants and enrolled CKD patients.

Abundance in Group 1: increased abundance in Chronic Kidney Disease

NCBI	Quality Control	Links
Bacteroides stercoris
Escherichia marmotae
Fusobacterium mortiferum
Limosilactobacillus mucosae
Streptococcus pasteurianus
Subdoligranulum variabile
Culturomica massiliensis

Revision editor(s): PreciousMike, Ayibatari

Signature 2

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Source: Figure 3

Description: Classification of operational taxonomy unit (OTU) with long-read sequencing in healthy participants and enrolled CKD patients.

Abundance in Group 1: decreased abundance in Chronic Kidney Disease

NCBI	Quality Control	Links
Anaerostipes hadrus
Selenomonas ruminantium
Mitsuokella jalaludinii
Megasphaera indica

Revision editor(s): PreciousMike, Ayibatari

Experiment 2

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Curated date: 2024/03/23

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Differences from previous experiment shown

Subjects

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Chronic kidney disease patients without comorbidities

Group 1 sample size Number of subjects in the case (exposed) group: 40

Lab analysis

Statistical Analysis

Alpha Diversity

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

Simpson Estimator of species richness and species evenness: more weight on species evenness: increased

Experiment 3

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Curated date: 2024/03/23

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Differences from previous experiment shown

Subjects

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Hypertensive chronic kidney disease patients

Group 1 sample size Number of subjects in the case (exposed) group: 26

Lab analysis

Statistical Analysis

Alpha Diversity

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

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Experiment 4

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Curated date: 2024/03/23

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Differences from previous experiment shown

Subjects

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Diabetic chronic kidney disease patients