Diaz Patricia I, Hong Bo-Young, Dupuy Amanda K, Choquette Linda, Thompson Angela, Salner Andrew L, Schauer Peter K, Hegde Upendra, Burleson Joseph A, Strausbaugh Linda D, Peterson Douglas E, Dongari-Bagtzoglou Anna
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.
J Fungi (Basel). 2019 Jun 13;5(2):49. doi: 10.3390/jof5020049.
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 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 . Oral candidiasis was not found to be associated with mycobiome structure shifts during the cycle but was the result of an increase in load, with and 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.
口腔念珠菌病是癌症化疗的常见副作用。为了更好地了解易感因素，我们对45名接受基于5-氟尿嘧啶或阿霉素治疗的受试者进行了一个化疗周期的随访。在基线、首次输注前以及两周内的另外三次就诊时对受试者进行评估。我们评估了人口统计学、医学和口腔健康参数、中性粒细胞监测，并通过扩增子高通量测序对唾液细菌群落和真菌群落进行了特征分析。所有受试者中有20%发生了口腔念珠菌病。通过多变量统计分析，我们确定吸烟、牙菌斑量、细菌群落和真菌群落的低α多样性以及特定细菌和真菌类群的比例是治疗周期中口腔念珠菌病发生的基线预测因素。所有发生口腔念珠菌病的受试者的基线微生物群落均以嗜酸菌为主且嗜酸菌丰富。从纵向来看，口腔念珠菌病与病变发生前唾液流量的减少有关，并且与口腔黏膜炎同时发生或在其之前发生。念珠菌病在纵向也与外周血中性粒细胞减少有关，但增加了中性粒细胞的杀伤能力。未发现念珠菌病与周期中的真菌群落结构变化有关，而是由负荷增加导致的，其中和是受影响受试者唾液真菌群落中最丰富的物种。总之，我们确定了一组与口腔念珠菌病易感性相关的临床和微生物群落基线因素，这可能是在化疗前识别高危个体的有用工具。
