title: Changes of saliva microbiota in nasopharyngeal carcinoma patients under chemoradiation therapy.
abstract: OBJECTIVE
  A growing body of evidence has implicated human oral microbiota in the aetiology of oral and systemic diseases. Nasopharyngeal carcinoma (NPC), an epithelial-originated malignancy, has a complex aetiology not yet fully understood. Chemoradiation therapy of NPC can affect oral microbiota and is usually accompanied by plaque accumulation. Thus, the study aimed to understand the diversity, divergence and development of the oral microbiota in NPC patients and their associated treatment, which might provide useful insights into disease aetiology and treatment side effects.
  
  
  METHODS
  A longitudinal study was designed that included three Chinese adults with NPC. Saliva samples were collected at three time points: prior to the chemoradiation treatment (carcinoma baseline, or CB), 7 months post-treatment (carcinoma-after-therapy phase 1 or CA1) and 12 months post-treatment (carcinoma-after-therapy phase 2 or CA2). Pyrosequencing of the bacterial 16S ribosomal DNA (rDNA) V1-V3 hypervariable region was employed to characterise the microbiota. Saliva samples of three healthy subjects from our former study were employed as healthy controls. Principal coordinates analysis (PCoA), Metastats and random forest prediction models were used to reveal the key microbial members associated with NPC and its treatment programme.
  
  
  RESULTS
  (1) In total, 412 bacterial species from at least 107 genera and 13 phyla were found in the saliva samples of the NPC patients. (2) PCoA revealed that not only were the microbiota from NPC patients distinct from those of healthy controls (p<0.001) but also that separation was found on the saliva microbiota between pre- and post-therapy (p<0.001) in the NPC samples. (3) At the genus level and the operational taxonomic unit (OTU) level, Streptococcus was found with lower abundance in NPC samples. (4) Chemoradiation therapy did not incur similar changes in microbiota structure among the three NPC patients; the microbiota in one of them stayed largely steady, while those in the other two showed significant alteration.
  
  
  CONCLUSIONS
  This is the first study employing culture-independent techniques to interrogate the phylogenetic diversity, divergence and temporal development of oral microbiota in NPC patients. Our results indicated that certain bacterial taxa might be associated with NPC and that oral microbiota of NPC patients might respond to the chemoradiation therapy in a host-specific manner. Further investigation with larger sample size should help to validate the links between oral microbiota and NPC.
authors.affiliation: Department of Stomatology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. Electronic address: xuyuan@sysucc.org.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Teng
authors.affiliation: Bioenergy Genome Center, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Zhengmei
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Oral Research Center, Qingdao Municipal Hospital, Qingdao, Shandong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Bioenergy Genome Center, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Oral Research Center, Qingdao Municipal Hospital, Qingdao, Shandong, China. Electronic address: yangf82@sina.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
mesh_terms: D000328:Adult; D002277:Carcinoma; D059248:Chemoradiotherapy; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D064307:Microbiota / Q000235:genetics* / Q000528:radiation effects; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000382:microbiology* / Q000628:therapy*; D016133:Polymerase Chain Reaction; D012463:Saliva / Q000382:microbiology*
chemical_list: D004269:DNA, Bacterial
keywords: Nasopharyngeal carcinoma; Oral microbiota; Pyrosequencing; Radiation therapy; Saliva