Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Chandrasekaran P, Han Y, Zerbe CS, Heller T, DeRavin SS, Kreuzberg SA, Marciano BE, Siu Y, Jones DR, Abraham RS, Stephens MC, Tsou AM, Snapper S, Conlan S, Subramanian P, Quinones M, Grou C, Calderon V, Deming C, Leiding JW, Arnold DE, Logan BR, Griffith LM, Petrovic A, Mousallem TI, Kapoor N, Heimall JR, Barnum JL, Kapadia M, Wright N, Rayes A, Chandra S, Broglie LA, Chellapandian D, Deal CL, Grunebaum E, Lim SS, Mallhi K, Marsh RA, Murguia-Favela L, Parikh S, Touzot F, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Kang EM, Malech HL, Segre JA, Bryant CE, Holland SM, Falcone EL
Journal
The Journal of allergy and clinical immunology
Year
2023
Keywords:
CGD, Chronic granulomatous disease, IBD, NADPH oxidase, dysbiosis, inborn errors of immunity, inflammatory bowel disease, intestinal inflammation, metabolome, microbiome, primary immune deficiency
BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.
Experiment 4
Differences from previous experiment shown
Subjects
- Location of subjects
- Canada
- United States of America
- 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
- Cohort Cohort,cohort
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- PIDTC Cohort (CGD without IBD)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NIHCC Cohort (CGD without IBD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Chronic granulomatous disease (CGD) without a history of Inflammatory bowel disease (IBD) and not receiving any medications other than prophylactic antimicrobials.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 23
- Group 1 sample size Number of subjects in the case (exposed) group
- 16
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Recent treatment with nonprophylactic antibiotics (acute antibiotics)
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- 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).
- 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
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig 3
Description: Comparison of microbiome signatures between patients with CGD (without a history of IBD) from NIHCC and PIDTC cohorts using LEfSe
Abundance in Group 1: decreased abundance in NIHCC Cohort (CGD without IBD)
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus |
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig 3
Description: Comparison of microbiome signatures between patients with CGD (without a history of IBD) from NIHCC and PIDTC cohorts using LEfSe
Abundance in Group 1: increased abundance in NIHCC Cohort (CGD without IBD)
Experiment 5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- PIDTC Cohort (CGD Patients)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NIHCC Cohort (CGD Patients)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Chronic granulomatous disease (CGD) regardless of IBD status or antimicrobial use
- Group 0 sample size Number of subjects in the control (unexposed) group
- 36
- Group 1 sample size Number of subjects in the case (exposed) group
- 79
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Recent treatment with non prophylactic antibiotics (acute antibiotics)
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig E4
Description: Comparison of microbiome signatures between patients with CGD (regardless of IBD status) from NIHCC and PIDTC cohorts using LEfSe
Abundance in Group 1: decreased abundance in NIHCC Cohort (CGD Patients)
| NCBI | Quality Control | Links |
|---|---|---|
| Butyricicoccus | ||
| Streptococcus |
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig E4
Description: Description: Comparison of microbiome signatures between patients with CGD (regardless of IBD status) from NIHCC and PIDTC cohorts using LEfSe
Abundance in Group 1: increased abundance in NIHCC Cohort (CGD Patients)
Experiment 6
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Age Age,age
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CGD patients less than or equal to 12 years
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CGD patients above 12 years
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- CGD patients above 12 years old with no active IBD or history of IBD
- Group 0 sample size Number of subjects in the control (unexposed) group
- 26
- Group 1 sample size Number of subjects in the case (exposed) group
- 12
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Chao1 Abundance-based estimator of species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-4-9
Source: Fig E5
Description: Effect of age on microbiome signatures in CGD patients (with no active IBD or history of IBD) comparing participants less than or equal to 12 years and above 12 years using LEfSe
Abundance in Group 1: increased abundance in CGD patients above 12 years
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes | ||
| Bilophila | ||
| Butyricicoccus | ||
| Oscillibacter | ||
| Sellimonas | ||
| Subdoligranulum | ||
| [Ruminococcus] torques | ||
| Lachnospiraceae bacterium NK4A136 |
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