Gut Microbiome Composition Predicts Infection Risk During Chemotherapy in Children With Acute Lymphoblastic Leukemia
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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
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.
Statistical test
Negative Binomial Regression
Experiment 1
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
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
- 87
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
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- 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
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Source: 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 | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Clostridiaceae | ||
| Streptococcaceae | ||
| Enterococcaceae | ||
| Lactobacillaceae |
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Source: 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 | Quality Control | Links |
|---|---|---|
| Faecalibacterium sp. | ||
| Actinomycetota | ||
| Verrucomicrobiota |
Experiment 2
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Differences from previous experiment shown
Subjects
- 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 1 sample size Number of subjects in the case (exposed) group
- 107
Lab analysis
Statistical Analysis
- 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
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Source: 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 | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Lactobacillaceae |
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
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 | Quality Control | Links |
|---|---|---|
| Bacteroidota | ||
| Actinomycetota | ||
| Verrucomicrobiota |
Experiment 3
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Differences from previous experiment shown
Subjects
- 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 1 sample size Number of subjects in the case (exposed) group
- 90
Lab analysis
Statistical Analysis
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
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Source: 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 | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Clostridiaceae | ||
| Enterococcaceae | ||
| Lactobacillaceae |
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Source: 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 | Quality Control | Links |
|---|---|---|
| Oscillospiraceae | ||
| Faecalibacterium sp. | ||
| Actinomycetota | ||
| Verrucomicrobiota |
Experiment 4
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
Differences from previous experiment shown
Subjects
- 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
- 47
- Group 1 sample size Number of subjects in the case (exposed) group
- 65
Lab analysis
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-8-17
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 | Quality Control | Links |
|---|---|---|
| Pseudomonadota |
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