TY - JOUR
T1 - Observational cohort study of oral mycobiome and interkingdom interactions over the course of induction therapy for leukemia
AU - Robinson, Sarah
AU - Peterson, Christine B.
AU - Sahasrabhojane, Pranoti
AU - Ajami, Nadim J.
AU - Shelburne, Samuel A.
AU - Kontoyiannis, Dimitrios P.
AU - Galloway-Peña, Jessica R.
N1 - Funding Information:
This work was supported by the MD Anderson Cancer Center Knowledge Gap and Multidisciplinary Research Program funding mechanisms (D.P.K. and S.A.S.). J.R.G.-P. was supported by the MD Anderson Odyssey Fellowship Program and the CFP Foundation for part of the duration of this work as well as by the NIH (1 K01 AI143881-01 from the NIAID). C.B.P. is partially supported by NIH/NCI Cancer Center support grant P30CA016672 (Biostatistics Resource Group). D.P.K. is supported by the Texas 4000 Distinguished Professorship for Cancer Research. This material is based upon work partially supported by the National Science Foundation Graduate Research Fellowship Program under grant no. 1842494 to S.R. Any opinions, findings, and conclusions or recommendations expressed in this material are ours and do not necessarily reflect the views of the National Science Foundation. We have no relevant disclosures with respect to conflicts of interest.
Publisher Copyright:
© 2020 Robinson et al.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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 remissioninduction 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 ±-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 ±-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.
AB - 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 remissioninduction 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 ±-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 ±-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.
KW - Induction chemotherapy
KW - Interkingdom interactions
KW - Leukemia
KW - Malassezia
KW - Mycobiome
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U2 - 10.1128/MSPHERE.00048-20
DO - 10.1128/MSPHERE.00048-20
M3 - Article
C2 - 32295867
AN - SCOPUS:85083478804
SN - 2379-5042
VL - 5
JO - mSphere
JF - mSphere
IS - 2
M1 - 04820
ER -