Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease

From BugSigDB
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6
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 1


Needs review

Curated date: 2024/03/09

Curator: Ifyohondu

Revision editor(s): Ifyohondu

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
Chronic granulomatous disease Bridges-Good syndrome,CGD,chronic granulomatous disease,Chronic septic granulomatosis,chronic septic granulomatosis,congenital dysphagocytosis,granulomatous disease, chronic,Quie syndrome,Chronic granulomatous 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 granulomatous disease
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Chronic granulomatous disease and only receiving prophylactic antimicrobials and without a history of inflammatory bowel disease at the time of stool collection
Group 0 sample size Number of subjects in the control (unexposed) group
16
Group 1 sample size Number of subjects in the case (exposed) group
17
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
2.5
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
inflammatory bowel disease, antibiotic, antimicrobial agent

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-4-9

Curated date: 2024/03/14

Curator: Ifyohondu

Revision editor(s): Ifyohondu

Source: Fig 2

Description: Difference between the intestinal microbiome of patients with Chronic granulomatous disease and healthy controls by LEfSe.

Abundance in Group 1: increased abundance in Chronic granulomatous disease

NCBI Quality ControlLinks
Lachnoclostridium
Sellimonas
Thomasclavelia
Veillonella
uncultured Roseburia sp.
uncultured bacterium

Revision editor(s): Ifyohondu

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-4-9

Curated date: 2024/03/14

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Folakunmi

Source: Fig 2

Description: Difference between the intestinal microbiome of patients with Chronic granulomatous disease and healthy controls by LEfSe .

Abundance in Group 1: decreased abundance in Chronic granulomatous disease

NCBI Quality ControlLinks
Anaerostipes
Butyricicoccus sp.
Clostridium
Collinsella
Coprococcus
Dorea
Eubacterium ventriosum
Intestinimonas butyriciproducens
Lachnospira
Lachnospira eligens
Roseburia hominis
Turicibacter
uncultured Erysipelotrichaceae bacterium
uncultured Eubacterium sp.
uncultured Lachnospira sp.
uncultured Lachnospiraceae bacterium

Revision editor(s): Ifyohondu, Folakunmi

Experiment 2


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6

Curated date: 2024/05/06

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy individuals
Group 1 name Corresponds to the case (exposed) group for case-control studies
Chronic granulomatous disease (CGD) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
CGD patients without a history of IBD and only receiving prophylactic antimicrobials
Group 0 sample size Number of subjects in the control (unexposed) group
17
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)
N/A

Lab analysis

Statistical Analysis

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6

Curated date: 2024/05/06

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Fig. 2G

Description: Comparison of microbiome signatures between patients with CGD (without a history of IBD) VS Healthy individuals using LEfSe

Abundance in Group 1: increased abundance in Chronic granulomatous disease (CGD) patients

NCBI Quality ControlLinks
uncultured Roseburia sp.
uncultured bacterium

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6

Curated date: 2024/05/06

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Fig. 2G

Description: Comparison of microbiome signatures between patients with CGD (without a history of IBD) VS Healthy individuals using LEfSe

Abundance in Group 1: decreased abundance in Chronic granulomatous disease (CGD) patients

NCBI Quality ControlLinks
Butyricicoccus
Lachnospira eligens
uncultured bacterium
uncultured Lachnospiraceae bacterium
Intestinimonas butyriciproducens
Roseburia hominis

Revision editor(s): ChiomaBlessing

Signature 3

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6

Curated date: 2024/05/06

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Fig. 2G

Description: Comparison of microbiome signatures between patients with CGD (without a history of IBD) VS Healthy individuals using LEfSe

Abundance in Group 1: increased abundance in Chronic granulomatous disease (CGD) patients

NCBI Quality ControlLinks
uncultured Roseburia sp.
uncultured bacterium

Revision editor(s): ChiomaBlessing

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6

Curated date: 2024/03/18

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Victoria

Differences from previous experiment shown

Subjects

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
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

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

Curated date: 2024/03/18

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Source: Fig. 3C

Description: Comparison of microbiome signatures between patients with CGD (without a history of IBD) from NIHCC VS PIDTC cohorts using LEfSe

Abundance in Group 1: decreased abundance in NIHCC Cohort (CGD without IBD)

NCBI Quality ControlLinks
Enterococcus

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-4-9

Curated date: 2024/03/18

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Source: Fig. 3C

Description: Comparison of microbiome signatures between patients with CGD (without a history of IBD) from NIHCC VS PIDTC cohorts using LEfSe

Abundance in Group 1: increased abundance in NIHCC Cohort (CGD without IBD)

NCBI Quality ControlLinks
Agathobacter
Anaerostipes
Bacteroides
Butyricicoccus
Dorea
Faecalibacterium
Lachnospiraceae bacterium NK4A136
Monoglobus
Roseburia
Ruminococcus
Sellimonas
Subdoligranulum
[Ruminococcus] torques
Incertae_SedisIncertae_Sedis

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Experiment 5


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6

Curated date: 2024/03/19

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Victoria

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

Curated date: 2024/03/19

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Source: Fig E4C

Description: Comparison of microbiome signatures between patients with CGD (regardless of IBD status) from NIHCC VS PIDTC cohorts using LEfSe

Abundance in Group 1: decreased abundance in NIHCC Cohort (CGD Patients)

NCBI Quality ControlLinks
Butyricicoccus
Streptococcus

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-4-9

Curated date: 2024/03/19

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Source: Fig E4C

Description: Comparison of microbiome signatures between patients with CGD (regardless of IBD status) from NIHCC VS PIDTC cohorts using LEfSe

Abundance in Group 1: increased abundance in NIHCC Cohort (CGD Patients)

NCBI Quality ControlLinks
Agathobacter
Clostridiales bacterium DTU089
Faecalicatena fissicatena
Lachnospiraceae bacterium NK4A136
Monoglobus
Moryella
Oscillibacter
Sellimonas
Subdoligranulum
[Ruminococcus] torques
Incertae _SedisIncertae _Sedis
uncultureduncultured

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Experiment 6


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-5-6

Curated date: 2024/03/19

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Victoria

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

Curated date: 2024/03/19

Curator: Ifyohondu

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing

Source: Fig E5D

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 VS above 12 years using LEfSe

Abundance in Group 1: increased abundance in CGD patients above 12 years

NCBI Quality ControlLinks
Alistipes
Bilophila
Butyricicoccus
Lachnospiraceae bacterium NK4A136
Oscillibacter
Sellimonas
Subdoligranulum
[Ruminococcus] torques

Revision editor(s): Ifyohondu, Folakunmi, ChiomaBlessing