Oral microbiome and mycobiome dynamics in cancer therapy-induced oral mucositis

Abstract

Cancer therapy-induced oral mucositis is a frequent major oncological problem, secondary to cytotoxicity of chemo-radiation treatment. Oral mucositis commonly occurs 7-10 days after initiation of therapy; it is a dose-limiting side effect causing significant pain, eating difficulty, need for parenteral nutrition and a rise of infections. The pathobiology derives from complex interactions between the epithelial component, inflammation, and the oral microbiome. Our longitudinal study analysed the dynamics of the oral microbiome (bacteria and fungi) in nineteen patients undergoing chemo-radiation therapy for oral and oropharyngeal squamous cell carcinoma as compared to healthy volunteers. The microbiome was characterized in multiple oral sample types using rRNA and ITS sequence amplicons and followed the treatment regimens. Microbial taxonomic diversity and relative abundance may be correlated with disease state, type of treatment and responses. Identification of microbial-host interactions could lead to further therapeutic interventions of mucositis to re-establish normal flora and promote patients' health. Data presented here could enhance, complement and diversify other studies that link microbiomes to oral disease, prophylactics, treatments, and outcome.

Fig. 1

Longitudinal sampling design for control and cancer subjects. Saliva (S), oral mucosa swab samples from tumour (T) or normal site (N) were collected at weeks 0, 2, 7 and 11. The number indicate absence (0, no shading) or presence (shaded) of mucositis of various grades (1,2,3) and/or thrush (x). Administration of anti-fungal medication is indicated by the star symbols. The cartoons summarize the type of collected samples.

Fig. 2

Microbiome diversity in healthy controls and cancer subjects. The most relatively abundant bacteria and fungi identified in healthy and cancer subjects were averaged across all sample types and timepoints for healthy subjects. For cancer subjects, data was averaged for weeks 0 and 7, respectively.

Fig. 3

Microbiome alpha diversity. Shannon alpha diversity was calculated for healthy control and cancer cohorts for each sampling timepoint.