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Open AccessArticle

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

Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT 06030, USA
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA
Department of Medical Oncology, Hartford Healthcare, Hartford, CT 06106, USA
Department of Medicine, UConn Health, Farmington, CT 06030, USA
Department of Community Medicine and Health Care, UConn Health, Farmington, CT 06032, USA
Authors to whom correspondence should be addressed.
J. Fungi 2019, 5(2), 49;
Received: 27 May 2019 / Revised: 11 June 2019 / Accepted: 12 June 2019 / Published: 13 June 2019
(This article belongs to the Special Issue Oral Mycobiome)
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 Candida 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 Candida albicans. Oral candidiasis was not found to be associated with mycobiome structure shifts during the cycle but was the result of an increase in Candida load, with C. albicans and Candida dubliniensis 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. View Full-Text
Keywords: oral candidiasis; microbiome; cancer chemotherapy; risk factors oral candidiasis; microbiome; cancer chemotherapy; risk factors
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Diaz, P.I.; Hong, B.-Y.; Dupuy, A.K.; Choquette, L.; Thompson, A.; Salner, A.L.; Schauer, P.K.; Hegde, U.; Burleson, J.A.; Strausbaugh, L.D.; Peterson, D.E.; Dongari-Bagtzoglou, A. Integrated Analysis of Clinical and Microbiome Risk Factors Associated with the Development of Oral Candidiasis during Cancer Chemotherapy. J. Fungi 2019, 5, 49.

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