The Effect of Intensity-Modulated Radiotherapy to the Head and Neck Region on the Oral Innate Immune Response and Oral Microbiome: A Prospective Cohort Study of Head and Neck Tumour Patients

Abstract

Neutrophils, also known as polymorphonuclear leukocytes (PMNs), form a significant component of the innate host response, and the consequence of the interaction between the oral microbiota and PMNs is a crucial determinant of oral health status. The impact of radiation therapy (RT) for head and neck tumour (HNT) treatment on the oral innate immune system, neutrophils in particular, and the oral microbiome has not been thoroughly investigated. Therefore, the objective of this study was to characterize RT-mediated changes in oral neutrophils (oPMNs) and the oral microbiome in patients undergoing RT to treat HNTs. Oral rinse samples were collected prior to, during and post-RT from HNT patients receiving RT at Dental Oncology at Princess Margaret Cancer Centre. The oPMNs counts and activation states were analysed using flow cytometry, and the oral microbiome was analysed using 16S rRNA gene sequencing. Statistically significant (p < 0.05) drops in oPMN counts and the activation states of the CD11b, CD16, CD18, CD64 and H3Cit markers from pre-RT to post-RT were observed. Moreover, exposure to RT caused a significant reduction in the relative abundance of commensal Gram-negative bacteria and increased the commensal Gram-positive microbes. Ionizing radiation for the treatment of HNTs simultaneously decreased the recruitment of oPMNs into the oral cavity and suppressed their activation state. The oral microbiome composition post-RT was altered significantly due to RT which may favour the colonization of specific microbial communities unfavourable for the long-term development of a balanced oral microbiome.

A Longitudinal Metagenomic Comparative Analysis of Oral Microbiome Shifts in Patients Receiving Proton Radiation Versus Photon Radiation for Head and Neck Cancer

“…In fact, it has been shown that IMRT for head and neck cancer can lead to dysbiosis of the oral microbiome. [ 4 , 5 , 26 ] Consequently, an oral dysbiotic state and direct insult from the effects of radiation therapy may increase the risk of highly morbid radiation-induced iatrogenic conditions such as oral mucositis and radiation-induced salivary hypofunction. Resultant shifts in the diversity and species richness of the oral microbiome composition as a consequence of irradiation could potentially allow for the emergence of putative pathogens.…”

“…It has been established that IMRT for head and neck cancer can lead to dysbiosis of the oral microbiome. [ 4 , 5 ] Consequently, an oral dysbiotic state and direct insult from the effects of radiation therapy may increase the risk of highly morbid radiation-induced iatrogenic conditions such as oral mucositis and radiation-induced salivary hypofunction and xerostomia. Resultant shifts in the diversity and species richness of the oral microbiome composition as a consequence of irradiation could potentially allow for the emergence of putative pathogens, prolong oral mucositis, prolong acute and long-term oral toxicities, and predispose to oral infections with a risk of life-threatening bacteremia, often necessitating antimicrobials and prolonging in-patient hospitalization.…”

Anti-cancer management of head and neck cancers and oral microbiome—what can we clinically obtain?

“…was reported in a case of oral cancer prior to radiotherapy, whereas Klebsiella and Pediococcus species as well as C. albicans were detected in the post-radiotherapy period (Anjali et al, 2020). In another prospective cohort study, it was observed that the number of commensal Gram-negative bacteria was reduced after exposure to radiation in the head and neck region (Mojdami et al, 2022). Schuurhuis et al investigated the changes in microbe composition depending on the methods of treatment (total patients n = 82; n = 29 surgical treatment, n = 26 intensive modulated radiation therapy, n = 27 intensive modulated radiation therapy in combination with chemotherapy) (Schuurhuis et al, 2016).…”

“…was reported in a case of oral cancer prior to radiotherapy, whereas Klebsiella and Pediococcus species as well as C. albicans were detected in the post-radiotherapy period ( Anjali et al., 2020 ). In another prospective cohort study, it was observed that the number of commensal Gram-negative bacteria was reduced after exposure to radiation in the head and neck region ( Mojdami et al., 2022 ). Schuurhuis et al.…”

The Role of the Innate Immune Response in Oral Mucositis Pathogenesis

“…During ulcerative mucositis progression, increased bacterial colonization at these sites causes unbalanced PAMPs and DAMPs, which trigger PRRmediated activation of downstream NF-κB signaling pathways, leading to augmented inflammatory responses due to the constant release of proinflammatory cytokines from innate immune cells [61]. The compositional changes to the oral microbiome observed across prior studies have varied, with reduction and expansion of differing microbial species being identified following treatment [71,72]. This varying nature of compositional analysis has led to suggestions that the resilience of the oral microbiome as well as the speed at which the microbial community is able to recover post-treatment may offer more reliable indicators for the impact of the oral microbiome on OM development and severity [73].…”