Observational Cohort Study of Oral Mycobiome and Interkingdom Interactions over the Course of Induction Therapy for Leukemia

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

32295867

DOI Digital object identifier for electronic documents.

10.1128/mSphere.00048-20

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

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-28

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing, Folakunmi, KateRasheed

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

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

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks, Atrayees, ChiomaBlessing, Folakunmi

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

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Malassezia

Revision editor(s): WikiWorks, Atrayees, ChiomaBlessing, Folakunmi

Experiment 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing, Folakunmi, KateRasheed

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

Lab analysis

Statistical Analysis

Statistical test

LEfSe

Signature 1

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Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks, Atrayees, ChiomaBlessing, Folakunmi

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

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Candida
Debaryomycetaceae
Saccharomycetales
Saccharomycetes

Revision editor(s): WikiWorks, Atrayees, ChiomaBlessing, Folakunmi

Experiment 3

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29

Curated date: 2023/12/01

Curator: Folakunmi

Revision editor(s): WikiWorks, ChiomaBlessing, Folakunmi, KateRasheed

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

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Curated date: 2023/12/01

Curator: Folakunmi

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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

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Fusarium
Nectriaceae
Sordariomycetes
Hypocreales
Fungi

Revision editor(s): Folakunmi, ChiomaBlessing, WikiWorks

Experiment 4

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-29

Curated date: 2023/12/01

Curator: Folakunmi

Revision editor(s): WikiWorks, ChiomaBlessing, Folakunmi, KateRasheed

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

Lab analysis

Statistical Analysis

Statistical test

ANOVA

Signature 1

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Curated date: 2023/12/01

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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

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Fusarium

Revision editor(s): Folakunmi, ChiomaBlessing, WikiWorks