Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy

Oral candidiasis is a common side effect of cancer chemotherapy. To better understand predisposing factors, we followed forty-five subjects who received 5-fluorouracil- or doxorubicin-based treatment, during one chemotherapy cycle. Subjects were evaluated at baseline, prior to the first infusion, an...

Full description

Bibliographic Details
Main Authors: Patricia I. Diaz, Bo-Young Hong, Amanda K. Dupuy, Linda Choquette, Angela Thompson, Andrew L. Salner, Peter K. Schauer, Upendra Hegde, Joseph A. Burleson, Linda D. Strausbaugh, Douglas E. Peterson, Anna Dongari-Bagtzoglou
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/5/2/49
_version_ 1818081262900871168
author Patricia I. Diaz
Bo-Young Hong
Amanda K. Dupuy
Linda Choquette
Angela Thompson
Andrew L. Salner
Peter K. Schauer
Upendra Hegde
Joseph A. Burleson
Linda D. Strausbaugh
Douglas E. Peterson
Anna Dongari-Bagtzoglou
author_facet Patricia I. Diaz
Bo-Young Hong
Amanda K. Dupuy
Linda Choquette
Angela Thompson
Andrew L. Salner
Peter K. Schauer
Upendra Hegde
Joseph A. Burleson
Linda D. Strausbaugh
Douglas E. Peterson
Anna Dongari-Bagtzoglou
author_sort Patricia I. Diaz
collection DOAJ
description Oral candidiasis is a common side effect of cancer chemotherapy. To better understand predisposing factors, we followed forty-five subjects who received 5-fluorouracil- or doxorubicin-based treatment, during one chemotherapy cycle. Subjects were evaluated at baseline, prior to the first infusion, and at three additional visits within a two-week window. We assessed the demographic, medical and oral health parameters, neutrophil surveillance, and characterized the salivary bacteriome and mycobiome communities through amplicon high throughput sequencing. Twenty percent of all subjects developed oral candidiasis. Using multivariate statistics, we identified smoking, amount of dental plaque, low bacteriome and mycobiome alpha-diversity, and the proportions of specific bacterial and fungal taxa as baseline predictors of oral candidiasis development during the treatment cycle. All subjects who developed oral candidiasis had baseline microbiome communities dominated by <i>Candida</i> and enriched in aciduric bacteria. Longitudinally, oral candidiasis was associated with a decrease in salivary flow prior to lesion development, and occurred simultaneously or before oral mucositis. Candidiasis was also longitudinally associated with a decrease in peripheral neutrophils but increased the neutrophil killing capacity of <i>Candida albicans</i>. Oral candidiasis was not found to be associated with mycobiome structure shifts during the cycle but was the result of an increase in <i>Candida</i> load, with <i>C. albicans</i> and <i>Candida dubliniensis</i> being the most abundant species comprising the salivary mycobiome of the affected subjects. In conclusion, we identified a set of clinical and microbiome baseline factors associated with susceptibility to oral candidiasis, which might be useful tools in identifying at risk individuals, prior to chemotherapy.
first_indexed 2024-12-10T19:03:25Z
format Article
id doaj.art-9af8c563c9714ef7beb4b783da3544ac
institution Directory Open Access Journal
issn 2309-608X
language English
last_indexed 2024-12-10T19:03:25Z
publishDate 2019-06-01
publisher MDPI AG
record_format Article
series Journal of Fungi
spelling doaj.art-9af8c563c9714ef7beb4b783da3544ac2022-12-22T01:36:58ZengMDPI AGJournal of Fungi2309-608X2019-06-01524910.3390/jof5020049jof5020049Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer ChemotherapyPatricia I. Diaz0Bo-Young Hong1Amanda K. Dupuy2Linda Choquette3Angela Thompson4Andrew L. Salner5Peter K. Schauer6Upendra Hegde7Joseph A. Burleson8Linda D. Strausbaugh9Douglas E. Peterson10Anna Dongari-Bagtzoglou11Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT 06030, USADepartment of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT 06030, USADepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USADepartment of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT 06030, USADepartment of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT 06030, USADepartment of Medical Oncology, Hartford Healthcare, Hartford, CT 06106, USADepartment of Medical Oncology, Hartford Healthcare, Hartford, CT 06106, USADepartment of Medicine, UConn Health, Farmington, CT 06030, USADepartment of Community Medicine and Health Care, UConn Health, Farmington, CT 06032, USADepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USADepartment of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT 06030, USADepartment of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT 06030, USAOral candidiasis is a common side effect of cancer chemotherapy. To better understand predisposing factors, we followed forty-five subjects who received 5-fluorouracil- or doxorubicin-based treatment, during one chemotherapy cycle. Subjects were evaluated at baseline, prior to the first infusion, and at three additional visits within a two-week window. We assessed the demographic, medical and oral health parameters, neutrophil surveillance, and characterized the salivary bacteriome and mycobiome communities through amplicon high throughput sequencing. Twenty percent of all subjects developed oral candidiasis. Using multivariate statistics, we identified smoking, amount of dental plaque, low bacteriome and mycobiome alpha-diversity, and the proportions of specific bacterial and fungal taxa as baseline predictors of oral candidiasis development during the treatment cycle. All subjects who developed oral candidiasis had baseline microbiome communities dominated by <i>Candida</i> and enriched in aciduric bacteria. Longitudinally, oral candidiasis was associated with a decrease in salivary flow prior to lesion development, and occurred simultaneously or before oral mucositis. Candidiasis was also longitudinally associated with a decrease in peripheral neutrophils but increased the neutrophil killing capacity of <i>Candida albicans</i>. Oral candidiasis was not found to be associated with mycobiome structure shifts during the cycle but was the result of an increase in <i>Candida</i> load, with <i>C. albicans</i> and <i>Candida dubliniensis</i> being the most abundant species comprising the salivary mycobiome of the affected subjects. In conclusion, we identified a set of clinical and microbiome baseline factors associated with susceptibility to oral candidiasis, which might be useful tools in identifying at risk individuals, prior to chemotherapy.https://www.mdpi.com/2309-608X/5/2/49oral candidiasismicrobiomecancer chemotherapyrisk factors
spellingShingle Patricia I. Diaz
Bo-Young Hong
Amanda K. Dupuy
Linda Choquette
Angela Thompson
Andrew L. Salner
Peter K. Schauer
Upendra Hegde
Joseph A. Burleson
Linda D. Strausbaugh
Douglas E. Peterson
Anna Dongari-Bagtzoglou
Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy
Journal of Fungi
oral candidiasis
microbiome
cancer chemotherapy
risk factors
title Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy
title_full Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy
title_fullStr Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy
title_full_unstemmed Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy
title_short Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy
title_sort integrated analysis of clinical and microbiome risk factors associated with the development of oral candidiasis during cancer chemotherapy
topic oral candidiasis
microbiome
cancer chemotherapy
risk factors
url https://www.mdpi.com/2309-608X/5/2/49
work_keys_str_mv AT patriciaidiaz integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT boyounghong integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT amandakdupuy integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT lindachoquette integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT angelathompson integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT andrewlsalner integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT peterkschauer integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT upendrahegde integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT josephaburleson integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT lindadstrausbaugh integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT douglasepeterson integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy
AT annadongaribagtzoglou integratedanalysisofclinicalandmicrobiomeriskfactorsassociatedwiththedevelopmentoforalcandidiasisduringcancerchemotherapy