Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-5-5
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Holle J, Bartolomaeus H, Löber U, Behrens F, Bartolomaeus TUP, Anandakumar H, Wimmer MI, Vu DL, Kuhring M, Brüning U, Maifeld A, Geisberger S, Kempa S, Schumacher F, Kleuser B, Bufler P, Querfeld U, Kitschke S, Engler D, Kuhrt LD, Drechsel O, Eckardt KU, Forslund SK, Thürmer A, McParland V, Kirwan JA, Wilck N, Müller D
Journal
Journal of the American Society of Nephrology : JASN
Year
2022
Keywords:
cardiovascular disease, children, chronic inflammation, chronic kidney disease, dysbiosis, hypertension, immunology, pediatric nephrology, vascular disease
BACKGROUND: CKD is characterized by a sustained proinflammatory response of the immune system, promoting hypertension and cardiovascular disease. The underlying mechanisms are incompletely understood but may be linked to gut dysbiosis. Dysbiosis has been described in adults with CKD; however, comorbidities limit CKD-specific conclusions. METHODS: We analyzed the fecal microbiome, metabolites, and immune phenotypes in 48 children (with normal kidney function, CKD stage G3-G4, G5 treated by hemodialysis [HD], or kidney transplantation) with a mean±SD age of 10.6±3.8 years. RESULTS: Serum TNF-α and sCD14 were stage-dependently elevated, indicating inflammation, gut barrier dysfunction, and endotoxemia. We observed compositional and functional alterations of the microbiome, including diminished production of short-chain fatty acids. Plasma metabolite analysis revealed a stage-dependent increase of tryptophan metabolites of bacterial origin. Serum from patients on HD activated the aryl hydrocarbon receptor and stimulated TNF-α production in monocytes, corresponding to a proinflammatory shift from classic to nonclassic and intermediate monocytes. Unsupervised analysis of T cells revealed a loss of mucosa-associated invariant T (MAIT) cells and regulatory T cell subtypes in patients on HD. CONCLUSIONS: Gut barrier dysfunction and microbial metabolite imbalance apparently mediate the proinflammatory immune phenotype, thereby driving the susceptibility to cardiovascular disease. The data highlight the importance of the microbiota-immune axis in CKD, irrespective of confounding comorbidities.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Subjects

Location of subjects
Germany
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 (HC)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Chronic Kidney Disease (CKD G3-G4)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Chronic Kidney Disease (CKD) stage G3–G4 and an eGFR of 15–60 ml/min per 1.73 m2.
Group 0 sample size Number of subjects in the control (unexposed) group
9
Group 1 sample size Number of subjects in the case (exposed) group
7
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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
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

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D and Supplementary Figure 2

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: increased abundance in Chronic Kidney Disease (CKD G3-G4)

NCBI Quality ControlLinks
Bacteroides
Parasutterella
Ruminococcus
Thomasclavelia
Clostridiales Vadin groupClostridiales Vadin group
Unknown genusUnknown genus
Cyanobacteriota

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: decreased abundance in Chronic Kidney Disease (CKD G3-G4)

NCBI Quality ControlLinks
Bacteroides
Parabacteroides
[Ruminococcus] torques
Ruminococacceae NK4A214Ruminococacceae NK4A214

Revision editor(s): MyleeeA

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Clinical treatment Clinical treatment,clinical treatment
Group 1 name Corresponds to the case (exposed) group for case-control studies
Hemodialysis (HD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Chronic Kidney Disease stage G5D, receiving maintenance Hemodialysis (HD), and enrolled at an earliest of 4 weeks after initiation of Hemodialysis (HD).
Group 1 sample size Number of subjects in the case (exposed) group
8

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: increased abundance in Hemodialysis (HD)

NCBI Quality ControlLinks
Acetanaerobacterium
Bacteroides
Barnesiella
Citrobacter
Dielma
Thomasclavelia

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D and Supplementary Figure 2

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: decreased abundance in Hemodialysis (HD)

NCBI Quality ControlLinks
Cyanobacteriota
Actinomycetota
Mycoplasmatota
Subdoligranulum
Tyzzerella
Fusicatenibacter
Bifidobacterium
Unknown genusUnknown genus

Revision editor(s): MyleeeA

Experiment 3


Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Kidney transplant Kidney transplant,kidney transplant
Group 1 name Corresponds to the case (exposed) group for case-control studies
Kidney transplantation (KT)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients after successful KT, at an earliest of 4 weeks after KT, without a history of rejection or chronic graft failure, and an eGFR of >60 ml/min per 1.73 m2

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D and Supplementary Figure 2

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: increased abundance in Kidney transplantation (KT)

NCBI Quality ControlLinks
Actinomycetota
Bifidobacterium
Parabacteroides
Bacteroides
Barnesiella

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: decreased abundance in Kidney transplantation (KT)

NCBI Quality ControlLinks
Ruminococcus

Revision editor(s): MyleeeA

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Clinical treatment Clinical treatment,clinical treatment
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Chronic Kidney Disease (CKD)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Hemodialysis (HD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Chronic Kidney Disease stage G5D, receiving maintenance Hemodialysis (HD), and enrolled at an earliest of 4 weeks after initiation of Hemodialysis (HD).
Group 0 sample size Number of subjects in the control (unexposed) group
7

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: increased abundance in Hemodialysis (HD)

NCBI Quality ControlLinks
Barnesiella
Escherichia/Shigella sp.

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D and Supplementary Figure 2

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: decreased abundance in Hemodialysis (HD)

NCBI Quality ControlLinks
Eubacterium coprostanoligenes
Fusicatenibacter
Ruminiclostridium
Tyzzerella
Ruminococcaceae UCG 013Ruminococcaceae UCG 013
Clostridiales vadin groupClostridiales vadin group
Unknown genusUnknown genus
Mycoplasmatota

Revision editor(s): MyleeeA

Experiment 5


Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

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
Kidney transplantation (KT)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Chronic Kidney Disease (CKD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Chronic Kidney Disease (CKD) stage G3–G4 and an eGFR of 15–60 ml/min per 1.73 m2.
Group 0 sample size Number of subjects in the control (unexposed) group
8
Group 1 sample size Number of subjects in the case (exposed) group
7

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: increased abundance in Chronic Kidney Disease (CKD)

NCBI Quality ControlLinks
Alistipes
Bacteroides
Eubacterium coprostanoligenes
Holdemanella
Parasutterella
Clostridiales vadin groupClostridiales vadin group

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: decreased abundance in Chronic Kidney Disease (CKD)

NCBI Quality ControlLinks
Bacteroides
Escherichia/Shigella sp.

Revision editor(s): MyleeeA

Experiment 6


Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/22

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Clinical treatment Clinical treatment,clinical treatment
Group 1 name Corresponds to the case (exposed) group for case-control studies
Hemodialysis (HD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Chronic Kidney Disease stage G5D, receiving maintenance Hemodialysis (HD), and enrolled at an earliest of 4 weeks after initiation of Hemodialysis (HD).
Group 1 sample size Number of subjects in the case (exposed) group
8

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: increased abundance in Hemodialysis (HD)

NCBI Quality ControlLinks
Alistipes
Bacteroides
Barnesiella
Butyricimonas
Faecalitalea
Prevotella

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-5-5

Curated date: 2025/04/23

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 2D and Supplementary Figure 2

Description: Taxonomic changes in the abundance of taxa on the genus, family, and phylum level. The heatmap shows significant changes in abundance using the DESeq2.

Abundance in Group 1: decreased abundance in Hemodialysis (HD)

NCBI Quality ControlLinks
Subdoligranulum
Ruminococcus
Cyanobacteriota
Ruminiclostridium
Unknown genusUnknown genus

Revision editor(s): MyleeeA