Longitudinal analysis of the oral microbial community during chemotherapy-induced mucositis in pediatric patients with hematological malignancies

The oral microbiome of cancer patients is subjected to several modulatory factors throughout cancer therapy. To what extent modulation of the oral microbiota contributes to the etiology or severity of oral mucositis is thus far not known. To this end, we performed a longitudinal study of the oral microbiota from five pediatric patients, treated with chemotherapy for hematological malignancies and suffering from oral mucositis. Saliva, buccal and mucositis lesions were sampled before and during chemotherapy over a 2-2.5 month period and after therapy as follow-up. Microbial community composition was determined with 16S rRNA gene based Illumina sequencing and correlations with clinical data were made. The oral microbial community displayed large dynamics throughout therapy in all patients, with patient-specific shifts. While Streptococcus was the predominant genus for 3 out of 5 patients, the other 2 patients showed a large variability in dominant genera over time, indicating a highly unbalanced microbiome. While the overall community composition seemed to return to its initial composition at least 1 month after therapy, a sustained impact towards lower diversity values was noted. Surprisingly, chemotherapy and mucositis had only a minor effect on microbial community composition, whereas one of the major confounding factors of our study was the use of systemic antibiotics as it majorly affected both microbial composition and diversity. Other confounding factors were sample type and sampling period, but also the use of antibacterial mouth rinse with chlorhexidine, neutropenia and inflammation. Mucositis lesions were highly dominated by Streptococci, but also by more pathogenic genera as Aggregatibacter, Enterococcus and Fusobacterium. In conclusion, this longitudinal analysis of the oral microbial community in pediatric cancer patients showed that despite large shifts in the oral microbial community of pediatric patients due to chemotherapeutic and antibiotic treatments, partial recovery occurs after therapy. Furthermore, these results support the importance of longitudinal analyses with long-term follow up after therapy and measurement of all confounding factors in future research.