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

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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


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
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

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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 ControlLinks
Fusarium
Candida
Saccharomyces
Cladosporium
Malassezia

Revision editor(s): Atrayees, WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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: decreased abundance in High Intensity Chemotherapy

NCBI Quality ControlLinks
Malassezia

Revision editor(s): Atrayees, WikiWorks

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

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

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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 ControlLinks
Candida

Revision editor(s): Atrayees, WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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 ControlLinks
Candida
Cladosporium
Fusarium
Malassezia
Saccharomyces

Revision editor(s): Atrayees, WikiWorks

Signature 3

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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 ControlLinks
Candida
Cladosporium
Fusarium
Malassezia
Saccharomyces

Revision editor(s): Atrayees, WikiWorks

Signature 4

Needs review

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Atrayees, WikiWorks

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 ControlLinks
Fusarium

Revision editor(s): Atrayees, WikiWorks