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
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-28
Curated date: 2021/01/10
Curator: WikiWorks
Revision editor(s): WikiWorks, Folakunmi, ChiomaBlessing
Subjects
- Location of subjects
- 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
- 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,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,Acute myeloid leukemia
- 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 receiving low-intensity remission induction chemotherapy at a later timepoint T6
- 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
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
Lab analysis
- Sequencing type
- ITS / ITS2
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- 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
- 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)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- decreased
Signature 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29
Curated date: 2021/01/10
Curator: William Lam
Revision editor(s): Atrayees, WikiWorks, Folakunmi, ChiomaBlessing
Source: Figure 4
Description: Significantly enriched taxa in patients who received high-intensity chemotherapies compared to those who received low-intensity chemotherapy
Abundance in Group 1: decreased abundance in High Intensity Chemotherapy
| NCBI | Quality Control | Links |
|---|---|---|
| Malassezia |
Revision editor(s): Atrayees, WikiWorks, Folakunmi, ChiomaBlessing
Experiment 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29
Curated date: 2021/01/10
Curator: WikiWorks
Revision editor(s): WikiWorks, Folakunmi, ChiomaBlessing
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Patients without bacterial infections at T3
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Patients with bacterial infections at T3
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Acute Myeloid Leukemia patients that experienced microbiologically defined bacterial infections during remission induction chemotherapy at midpoint timepoint T3
- 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
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29
Curated date: 2021/01/10
Curator: William Lam
Revision editor(s): Atrayees, WikiWorks, Folakunmi, ChiomaBlessing
Source: Figure S2 + Figure 6
Description: Differential abundance among acute leukemia patients who had infections during induction chemotherapy compared to those who did not experience infections at midpoint time point (T3)
Abundance in Group 1: increased abundance in Patients with bacterial infections at T3
| NCBI | Quality Control | Links |
|---|---|---|
| Candida | ||
| Debaryomycetaceae | ||
| Saccharomycetales | ||
| Saccharomycetes |
Revision editor(s): Atrayees, WikiWorks, Folakunmi, ChiomaBlessing
Experiment 3
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Patients with no bacterial infections at T6
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Patients with bacterial infections at T6
- 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 at endpoint timepoint T6
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29
Source: Figure 6 + Figure S3
Description: Differential abundance among acute leukemia patients who had infections during induction chemotherapy compared to those who did not experience infections at a later time point (T6)
Abundance in Group 1: decreased abundance in Patients with bacterial infections at T6
| NCBI | Quality Control | Links |
|---|---|---|
| Fusarium | ||
| Nectriaceae | ||
| Sordariomycetes | ||
| Hypocreales | ||
| Fungi |
Revision editor(s): Folakunmi, ChiomaBlessing
Experiment 4
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,Antimicrobial agent,antimicrobial agent
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Patients who did not receive Amphotericin B
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Patients who received Amphotericin B
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Acute Myeloid Leukemia patients who received amphotericin B.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 66
- Group 1 sample size Number of subjects in the case (exposed) group
- 6
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29
Source: Figure 5
Description: Effect of amphotericin B on the composition of the oral fungal community at T6 in those who received amphotericin B compared to those who did not
Abundance in Group 1: increased abundance in Patients who received Amphotericin B
| NCBI | Quality Control | Links |
|---|---|---|
| Fusarium |
Revision editor(s): Folakunmi, ChiomaBlessing
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