The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma

Abstract

BackgroundOral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis.MethodsBased on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated.FindingsOur results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema – patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89.InterpretationOral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.

Risk factors and implications of oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation

“…Although recent antibiotic use was not significant when incorporated into a multivariable analysis (RR 1.88 [95% CI: 0.77‐4.63]; P = .168), such an association may imply a potential role for the microbiota in OM development. Preliminary results from patients with head and neck malignancies treated with radiation indicate that the oral microbiota shift in patients who develop mucositis . Whether this change is correlative or causative is an area of active investigation.…”

“…However, current therapeutic approaches provide only limited protection. Our increasing understanding of mucositis pathophysiology, as well as the importance of shifts in salivary function, and the microbiota composition offers exciting new avenues for novel strategies.…”

“…30 In a randomized, phase III study of patients undergoing autologous HSCT, the incidence of severe OM was reduced from 98% to 63% (P = .001). 31 33,34 Whether this change is correlative or causative is an area of active investigation. There is strong biological rationale to postulate that the microbiome affects mucositis development: Commensal bacteria facilitate metabolic, and immune responses 35,36 and the pathophysiology of OM involve oxidative stress, the release of inflammatory cytokines, and activation of the innate immune system.…”

The Chicken or the Egg? Changes in Oral Microbiota as Cause or Consequence of Mucositis During Radiation Therapy

“…How, if, and where the oral microbiome contributes to this scheme was the subject of a study reported in this issue of EBioMedicine by Zhu et al (2017) who prospectively evaluated the relationship between the trajectory of changes in the oral microbiome and oral mucositis in nineteen patients being treated with radiation or concomitant chemoradiation for nasopharyngeal carcinoma (NPC). Thirteen of the studied subjects developed severe mucositis.…”

Role of intestinal dysbiosis on gut colonization by bacterial pathogens

“…However, some authors already reported that Saccharomyces cerevisiae significantly reduced E. coli O157:H7 growth in a dynamic multi-compartmental digestion system, possibly through a potential inhibitory role of ethanol produced by the yeast (149 Due to the low number of patients with mucositis and the variability of the microbiota among patients, we were not able to elucidate if mucositis was associated with specific changes in the microbiota that could promote MRE colonization. Taking into account a recent study reporting differences in the composition of the oral microbiota depending on the mucositis severity (154), it is likely that mucositis could also produce changes in the gut microbiota, which may impact MRE colonization levels. Further studies including more samples from patients developing mucositis should be necessary in order to elucidate a possible link between mucositis, microbiota and MRE colonization.…”