Observational Cohort Study of Oral Mycobiome and Interkingdom Interactions over the Course of Induction Therapy for 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
Robinson S, Peterson CB, Sahasrabhojane P, Ajami NJ, Shelburne SA, Kontoyiannis DP, Galloway-Peña JR
Journal
mSphere
Year
2020
Keywords:
Malassezia, induction chemotherapy, interkingdom interactions, leukemia, mycobiome
Although the term "microbiome" refers to all microorganisms, the majority of microbiome studies focus on the bacteriome. Here, we characterize the oral mycobiome, including mycobiome-bacteriome interactions, in the setting of remission-induction chemotherapy (RIC) for acute myeloid leukemia (AML). Oral samples (n = 299) were prospectively collected twice weekly from 39 AML patients during RIC until neutrophil recovery. Illumina MiSeq 16S rRNA gene (V4) and internal transcribed spacer 2 (ITS2) sequencing were used to determine bacterial and fungal diversity and community composition. Intrakingdom and interkingdom network connectivity at baseline (T1) and at midpoint (T3) and a later time point (T6) were assessed via SPIEC-EASI (sparse inverse covariance estimation for ecological association inference). In this exploratory study, mycobiome α-diversity was not significantly associated with antibiotic or antifungal receipt. However, postchemotherapy mycobiome α-diversity was lower in subjects receiving high-intensity chemotherapy. Additionally, greater decreases in Malassezia levels were seen over time among patients on high-intensity RIC compared to low-intensity RIC (P = 0.003). A significantly higher relative abundance of Candida was found among patients who had infection (P = 0.008), while a significantly higher relative abundance of Fusarium was found among patients who did not get an infection (P = 0.03). Analyses of intrakingdom and interkingdom relationships at T1, T3, and T6 indicated that interkingdom connectivity increased over the course of IC as bacterial α-diversity diminished. In (to our knowledge) the first longitudinal mycobiome study performed during AML RIC, we found that mycobiome-bacteriome interactions are highly dynamic. Our study data suggest that inclusion of mycobiome analysis in the design of microbiome studies may be necessary to optimally understand the ecological and functional role of microbial communities in clinical outcomes.IMPORTANCE This report highlights the importance of longitudinal, parallel characterization of oral fungi and bacteria in order to better elucidate the dynamic changes in microbial community structure and interkingdom functional interactions during the injury of chemotherapy and antibiotic exposure as well as the clinical consequences of these interrelated alterations.
Experiment 1
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
- Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- acute myeloid leukemia acute granulocytic leukemia,acute myeloblastic leukemia,acute myelocytic leukemia,acute myelogenous leukemia,acute myelogenous leukemias,acute myeloid leukemia,acute myeloid leukemia (AML),acute non lymphoblastic leukemia,acute Nonlymphocytic leukemia,acute nonlymphocytic leukemia,AML,AML - acute myeloid leukemia,ANLL,hematopoeitic - acute Myleogenous leukemia (AML),leukemia, acute myelogenous,leukemia, acute myeloid,leukemia, acute myeloid, susceptibility to,leukemia, myelocytic, acute,myeloid leukemia, acute
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low Intensity Chemotherapy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High Intensity Chemotherapy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Acute Myeloid Leukemia patients with receiving low- intensity remission induction chemotherapy
- Group 0 sample size Number of subjects in the control (unexposed) group
- 11
- Group 1 sample size Number of subjects in the case (exposed) group
- 28
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
- Statistical test
- ANOVA
- 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Needs review
Source: Figure S1 and text, Table S1, Figure 4
Description: Mycobiome characteristics correlate with chemotherapy intensity at later point of sample collection (T6)
Abundance in Group 1: increased abundance in High Intensity Chemotherapy
| NCBI | Quality Control | Links |
|---|---|---|
| Fusarium | ||
| Candida | ||
| Saccharomyces | ||
| Cladosporium | ||
| Malassezia |
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- No bacterial infections
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- bacterial infections
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Acute Myeloid Leukemia patients that experience microbiologically defined bacterial infections during remission induction chemotherapy
- Group 0 sample size Number of subjects in the control (unexposed) group
- 30
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
Lab analysis
Statistical Analysis
- Statistical test
- LEfSe
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
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
Source: Figure 6 and text, Table S2 and S3
Description: Relative abundance differences of taxa at individual time points among Acute Myeloid Leukemia patients who did and did not experience bacterial infection during remission induction chemotherapy at midpoint time point (T3) prior to neutrophil recovery
Abundance in Group 1: increased abundance in bacterial infections
| NCBI | Quality Control | Links |
|---|---|---|
| Candida |
Signature 2
Needs review
Source: Figure 6 and text, Table S2 and S3
Description: Relative abundance differences of taxa at individual time points among Acute Myeloid Leukemia patients who did and did not experience bacterial infection during remission induction chemotherapy at midpoint time point (T3) prior to neutrophil recovery
Abundance in Group 1: decreased abundance in bacterial infections
| NCBI | Quality Control | Links |
|---|---|---|
| Candida | ||
| Cladosporium | ||
| Fusarium | ||
| Malassezia | ||
| Saccharomyces |
Signature 3
Needs review
Source: Figure 6 and text, Table S2 and S3
Description: Relative abundance differences of taxa at individual time points among Acute Myeloid Leukemia patients who did and did not experience bacterial infection during remission induction chemotherapy at later time point (T6) prior to neutrophil recovery
Abundance in Group 1: increased abundance in bacterial infections
| NCBI | Quality Control | Links |
|---|---|---|
| Candida | ||
| Cladosporium | ||
| Fusarium | ||
| Malassezia | ||
| Saccharomyces |
Signature 4
Needs review
Source: Figure 6 and text, Table S2 and S3
Description: Relative abundance differences of taxa at individual time points among Acute Myeloid Leukemia patients who did and did not experience bacterial infection during remission induction chemotherapy at later time point (T6) prior to neutrophil recovery
Abundance in Group 1: decreased abundance in bacterial infections
| NCBI | Quality Control | Links |
|---|---|---|
| Fusarium |
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