E. Vanlancker ir, PhD, B. Vanhoecke PhD, B. De Moerloose MD, PhD, T. Van de Wiele ir, PhD
In this PhD thesis, we investigated the impact of chemotherapy on the microbiota in the context of mucositis by using different experimental set-ups. Using bacterial monocultures, we showed that exposure to 5-fluorouracil at physiologically relevant concentrations differentially impacts oral microorganisms. Despite this difference in microbial sensitivity to 5-fluorouracil in pure cultures, we showed that the impact of 5-fluorouracil, as well as irinotecan, towards highly diverse gastrointestinal microbial populations is only marginal. These findings were generated with two different model systems that exclude host cells and this led us to conclude that the host is crucial in the establishment of chemotherapy-induced shifts in microbial composition and functionality. The next step in our research entailed the use of an in vitro wound healing model, where we demonstrated that the presence of microbiota negatively impacts the wound healing capacity of damaged oral epithelial cells. This indicates that microbial presence can delay the recovery from mucositis. Yet, we also found that microbial composition, which is for instance disturbed in patients receiving cancer therapy, is an additional determinant of aggravated wound healing. We further substantiated this conclusion with an in vivo longitudinal monitoring study of paediatric patients treated for haematological malignancies. While shifts in the oral microbial community during and following chemotherapy were mostly patient-specific, clear associations were made with the use of systemic antibiotics and antibacterial mouth rinses, which create microbial dysbiosis. In view of these findings we propose that the preventive use of antimicrobials needs careful consideration given the profound impact on the microbiome and subsequent consequence for the host.