br Introduction Oral Oropharyngeal mucositis

Introduction Oral/Oropharyngeal mucositis (OM) is probably the most common and debilitating complication that can occur during and shortly after radiotherapy and/or chemotherapy for patients with head-and-neck cancer (HNC). It is typically characterized by: erythema, edema, mucosal ulceration and pseudomembrane formation in the oral cavity and oropharynx. Patients with OM lesions frequently complain of mild to severe pain and pharyngeal dysphagia. Currently, there are no effective mucoprotective strategies for the management of OM. Severe mucositis can not only affect a patients\' quality of life, but also increases the need for narcotic analgesics, total parenteral nutrition, interruption of cancer therapy, prolong hospitalization and increases the risk of local and systemic infection (Trotti et al., 2003; Villa and Sonis, 2015; Stokman et al., 2006). Recent studies have suggested that the pathogenesis of mucositis involves a cascade of inflammatory events, which chronologically consist of five continuous overlapping phases: initiation, upregulation of inflammation, signaling and amplification, ulceration, and finally wound healing (Sonis, 2004). Although it is hypothesized that genetic factors may correlate with an increased risk of developing mucositis (Venkatesh et al., 2014; Pratesi et al., 2011), the role of microorganisms in promoting inflammation and exacerbating mucositis still remains to be explored. Using culture-based techniques, several Gram-positive/negative species of bacteria were isolated from the oral cavity of patients undergoing radiochemotherapy in the head and neck region (Napenas et al., 2007; Almstahl et al., 2008; Panghal et al., 2012). Their normal bacterial pla2 inhibitor was significantly altered during the course of treatment, which leads naturally to the question as to whether changes in the oropharyngeal microflora may correlate with the onset and aggravation of OM. Unfortunately, there are so far no well-defined patterns with respect to these changes, and no consistent correlations were found between the presence of specific pathogens and the severity of OM. On the other hand, it is estimated that >700 bacterial species have been detected in the oral cavity, of which >50% remain to be cultivated (Aas et al., 2005). However, using culture-independent high-throughput 16S rRNA gene sequencing, it has been shown that changes in oral microbiota during radiochemotherapy are far more complicated than previously thought (Vanhoecke et al., 2015; Hu et al., 2013). Nevertheless, and more importantly until now, there has been few analysis made to our knowledge on the correlation between the OM severity and the dynamic changes it may make in bacterial profiles throughout radiochemotherapy.
Materials and Methods
Results
Discussion Nasopharyngeal carcinoma is one of the most common epithelial malignancies in Southern China (Guo et al., 2014). A number of theories regarding its pathogenesis have been proposed over the years (McDermott et al., 2001; Tsao et al., 2014). However, previously the possible role of oral and oropharyngeal bacteria in the development of NPC was rarely investigated. Thus it was of interest that we found healthy controls harbored more diverse and shared more similar bacterial communities than NPC patients. It is commonly believed that a stable and diverse microbiota is essential for several host physiological processes and mucosal immune functions, since in the oral cavity and oropharynx, the normal bacterial flora can prevent colonization by exogenous pathogens and overgrowth of indigenous pathobionts, whereas an altered composition of commensal flora, termed dysbiosis, could lead to immune dysregulation and increase a person\'s risk of developing several diseases (Tomkovich and Jobin, 2016). Moreover, compared to healthy individuals, our NPC patients harbored significantly greater abundances of Pseudomonas, Pediococcus and Oscillibacter in the oropharynx, all of which have been shown to be associated with human infections. Of particular note is the genus Pseudomonas that contains several nitrate- and/or nitrite-reducing bacteria, such as P. aeruginosa and P. fluorescens. These oral species can, in particular, endogenously synthesize N-nitroso compounds that are more commonly found in food samples from NPC high-risk areas (Feng et al., 2007) and represent a major class of important chemical carcinogens. In fact, the colonization of the nasopharynx by microflora that contain abundant nitrate-reducing microorganisms has been suggested to be a risk factor for NPC in Maghrebian populations (Charriere et al., 1991). Notwithstanding, it is questionable whether such changes in oropharyngeal bacterial profile are a cause or consequence of NPC. However to postulate further on this, is beyond the scope of this study.