Gut Microbiome Composition Predicts Infection Risk During Chemotherapy in Children With Acute Lymphoblastic Leukemia

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Hakim H, Dallas R, Wolf J, Tang L, Schultz-Cherry S, Darling V, Johnson C, Karlsson EA, Chang TC, Jeha S, Pui CH, Sun Y, Pounds S, Hayden RT, Tuomanen E, Rosch JW
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Year
2018
Background: Myelosuppression-related infections remain important causes of morbidity and mortality in children with acute lymphoblastic leukemia (ALL). Methods: By analyzing fecal samples collected at diagnosis and after each of the initial 3 phases of chemotherapy, we evaluated the role of gut microbiota in predicting infections in 199 children with newly diagnosed ALL. The bacterial 16S rRNA gene was analyzed by high-depth sequencing to determine the diversity and composition of the microbiome. Results: After the induction and reinduction I phases of chemotherapy, microbial diversity decreased significantly relative to the prechemotherapy value. After chemotherapy, the relative abundance of certain bacterial taxa (eg, Bacteroidetes) decreased significantly, whereas that of other taxa (eg, Clostridiaceae and Streptococcaceae) increased. A baseline gut microbiome characterized by Proteobacteria predicted febrile neutropenia. Adjusting for the chemotherapy phase and ALL risk level, Enterococcaceae dominance (relative abundance ≥30%) predicted significantly greater risk of subsequent febrile neutropenia and diarrheal illness, whereas Streptococcaceae dominance predicted significantly greater risk of subsequent diarrheal illness. Conclusions: In children undergoing therapy for newly diagnosed ALL, the relative abundance of Proteobacteria before chemotherapy initiation predicts development of febrile neutropenia, and domination of the gut microbiota by Enterococcaceae or Streptococcaceae at any time during chemotherapy predicts infection in subsequent phases of chemotherapy. Clinical Trial Registration: NCT00549848.

Experiment 1


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Suwaiba, 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
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
post-induction therapy
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
6 weeks of remission induction therapy
Group 0 sample size Number of subjects in the control (unexposed) group
112
Group 1 sample size Number of subjects in the case (exposed) group
97

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V3
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Negative Binomial Regression
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


Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
antibiotic exposure, demographics

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Table 1, Figure 1 and 2, Supplemental Table S3

Description: Change in gut microbiota diversity in acute lymphoblastic leukemia children from baseline to post induction

Abundance in Group 1: increased abundance in post-induction therapy

NCBI Links
Bacillota
Clostridiaceae
Streptococcaceae
Enterococcaceae
Lactobacillaceae

Revision editor(s): WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Table 1, Figure 1 and 2, Supplemental Table S3

Description: Change in gut microbiota diversity in acute lymphoblastic leukemia children from baseline to post induction

Abundance in Group 1: decreased abundance in post-induction therapy

NCBI Links
Bacteroidota
Faecalibacterium sp.
Oscillospiraceae
Actinomycetota
Verrucomicrobiota

Revision editor(s): WikiWorks

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Atrayees

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
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
post-consolidation therapy
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
8 weeks of consolidation
Group 0 sample size Number of subjects in the control (unexposed) group
112
Group 1 sample size Number of subjects in the case (exposed) group
107

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Negative Binomial Regression
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


Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "chemotherapy and acute lymphoblastic leukemia" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.chemotherapy and acute lymphoblastic leukemia

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Table 1, Figure 1 and 2, Supplemental Table S3

Description: Change in gut microbiota diversity in acute lymphoblastic leukemia children from baseline to postconsildation

Abundance in Group 1: increased abundance in post-consolidation therapy

NCBI Links
Bacillota
Blautia sp.
Clostridiaceae
Lactobacillaceae

Revision editor(s): WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Table 1, Figure 1 and 2, Supplemental Table S3

Description: Change in gut microbiota diversity in acute lymphoblastic leukemia children from baseline to postconsildation

Abundance in Group 1: decreased abundance in post-consolidation therapy

NCBI Links
Bacteroidota
Actinomycetota

Revision editor(s): WikiWorks

Experiment 3


Needs review

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
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
post re-induction therapy
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
120 weeks of continuation phase with the last 17-20 weeks of reinduction II therapy
Group 0 sample size Number of subjects in the control (unexposed) group
112
Group 1 sample size Number of subjects in the case (exposed) group
90

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
negative binomial regression Statistical test: "negative binomial regression" is not in the list (ANCOM, ANOSIM, ANOVA, DESeq2, edgeR, Fisher's Exact Test, Kruskall-Wallis, LEfSe, Linear Regression, Logistic Regression, ...) of allowed values.
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


Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "chemotherapy and acute lymphoblastic leukemia" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.chemotherapy and acute lymphoblastic leukemia

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Table 1, Figure 1 and 2, Supplemental Table S3

Description: Change in gut microbiota diversity in acute lymphoblastic leukemia children from baseline to post re-induction

Abundance in Group 1: increased abundance in post re-induction therapy

NCBI Links
Bacillota
Clostridiaceae
Enterococcaceae
Lactobacillaceae

Revision editor(s): WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Table 1, Figure 1 and 2, Supplemental Table S3

Description: Change in gut microbiota diversity in acute lymphoblastic leukemia children from baseline to post re-induction

Abundance in Group 1: decreased abundance in post re-induction therapy

NCBI Links
Oscillospiraceae
Faecalibacterium sp.
Actinomycetota
Verrucomicrobiota

Revision editor(s): WikiWorks

Experiment 4


Needs review

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
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
non-febrile neutropenia
Group 1 name Corresponds to the case (exposed) group for case-control studies
febrile neutropenia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
fever as an oral temperature more than 38.0°C persisting for more than 1 hour; neutropenia as an absolute neutrophil count less than or equal to 500 cells per microliter after baseline first sampled
Group 0 sample size Number of subjects in the control (unexposed) group
42
Group 1 sample size Number of subjects in the case (exposed) group
122

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
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


Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "chemotherapy and acute lymphoblastic leukemia" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.chemotherapy and acute lymphoblastic leukemia

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Supplemental Table S6, Figure 5a

Description: Comparison of baseline diversity and composition between acute lymphoblastic leukemia children with and without febrile neutropenia occurring throughout therapy

Abundance in Group 1: increased abundance in febrile neutropenia

NCBI Links
Pseudomonadota

Revision editor(s): WikiWorks