Caries-associated oral microbiome in head and neck cancer radiation patients: a longitudinal study

Jean-Luc C Mougeot, Craig B Stevens, Kathryn G Almon, Bruce J Paster, Rajesh V Lalla, Michael T Brennan, Farah Bahrani Mougeot, Jean-Luc C Mougeot, Craig B Stevens, Kathryn G Almon, Bruce J Paster, Rajesh V Lalla, Michael T Brennan, Farah Bahrani Mougeot

Abstract

Head and neck cancer (HNC) therapy often leads to caries development. Our goal was to characterize the oral microbiome of HNC patients who underwent radiation therapy (RT) at baseline (T0), and 6 (T6) and 18 (T18) months post-RT, and to determine if there was a relationship with increased caries. HOMINGS was used to determine the relative abundance (RA) of >600 bacterial species in oral samples of 31 HNC patients. The DMFS score was used to define patient groups with tooth decay increase (DMFS[+]) or no increase (DMFS[-]).A change in microbiome beta-diversity was observed at T6 and T18. The Streptococcus mutans RA increased at T6 in both DMFS[+] and DMFS[-] groups. The RA of Prevotella melaninogenica, the species often associated with caries in young children, decreased at T6 in the DMFS[-] group. The RA of the health-associated species, Abiotrophia defective, decreased in the DMFS[+] group. The oral microbiome underwent significant changes in radiation-treated HNC patients, whether they developed caries or not. Caries rates were not associated with a difference in salivary flow reduction between DMFS[+] andDMFS[-] groups. Patients who develop caries might be more susceptible to certain species associated with oral disease or have fewer potentially protective oral species.

Keywords: 16S rRNA; Head and neck cancer; caries; microbiome; next generation sequencing; radiation therapy.

Figures

Figure 1.
Figure 1.
Analytical design for the determination of oral microbiome beta-diversity changes in radiation-treated head and neck cancer patients. Comparisons of beta-diversity were carried out using transformed relative abundances (RA) or standardized RA fraction difference (RA-FD) to determine overall changes following radiation therapy (post-RT), changes occurring in clinically different subgroups, and changes characterizing DMFS[+] and DMFS[-] patients. Pts: HNC patients; T0: baseline time point prior to radiation therapy; Tx: T6 (6-months) or T18 (18-months) post-RT; AB: antibiotics; IC: Induction Chemotherapy; CC: Concurrent Chemotherapy. T0 to Tx corresponds to baseline to 6-months post-RT sampling (T0-T6), or baseline to 18-months post-RT sampling (T0-T18).
Figure 2.
Figure 2.
A significant oral microbiome profile shift occurs between T0 and T6 for all RT-treated HNC patients (a) and patients treated with RT and concurrent chemotherapy only (b). Timepoints: T0-pre-RT baseline sampling, T6-post-RT sampling at 6 months.
Figure 3.
Figure 3.
Non-metric multidimensional scaling (nMDS) of caries-associated species profiles of oral sites for all patients and patients who underwent concurrent chemotherapy (CC) T0 to Tx. a. T0-T6-All Patients (Subset-A; n = 28). b. T0-T18-All Patients (Subset-A; n = 20). c. T0-T6-Patients w/CC (Subset-D; n = 24). d. T0-T18-Patients w/CC (Subset-D; n = 19). A significant shift of caries-associated species profiles occurs between T0 to T6 (a, c), and T0 to T18 (b, d) for RT-treated HNC patients and for patients treated with RT and concurrent chemotherapy. T0 to Tx corresponds to baseline to 6-months post-RT sampling (T0-T6), or baseline to 18-months post-RT sampling (T0-T18).
Figure 4.
Figure 4.
Changes in relative abundance of caries- and health- associated species in DMFS[+] compared to DMFS[-] RT-treated HNC patients (Subset-D, all patients with CC). a. Caries-associated species. b. Health-associated species On the left of each chart, the T0 to T6 relative abundance (RA) change (Chg), i.e., T6 average RA minus T0 average RA by species is shown for the DMFS[+] and DMFS[-] groups of Subset-D, all HNC patients treated with RT and concurrent chemotherapy, for caries- (a) and health- (b) associated species. The difference in the group RA’s shown on the left, i.e., DMFS[+] average RA minus DMFS[-] average RA, by species is presented on the right of the charts. HOMINGS species probes identification 4-character codes are shown. A chi-squared test was used to determine the significance of differences in RA increases/decreases between the DMFS[+] and DMFS[-] groups. *p < 0.05; **p < 0.01; ***p < 0.001.

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