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...
Main Authors: | , , , , , , , , , , , |
---|---|
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 |