title: Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome.
abstract: OBJECTIVE
  Gastroesophageal reflux causes inflammation and intestinal metaplasia and its downstream sequelum adenocarcinoma in the distal esophagus. The incidence of esophageal adenocarcinoma has increased approximately 6-fold in the United States since the 1970s, accompanied with a significant increase in the prevalence of gastroesophageal reflux disease (GERD). Despite extensive epidemiologic study, the cause for GERD and the unexpected increases remain unexplainable. Microbes are among the environmental factors that may contribute to the etiology of GERD, but very little research has been done on the esophageal microbiome, particularly in its relation to GERD. This is the first comprehensive reported correlation between a change in the esophageal microbiome and esophageal diseases.
  
  
  METHODS
  Biopsy samples of the distal esophagus were collected from 34 patients. Host phenotypes were histologically defined as normal, esophagitis, or Barrett's esophagus (intestinal metaplasia). Microbiomes from the biopsy samples were analyzed by bacterial 16S ribosomal RNA gene survey and classified into types using unsupervised cluster analysis and phenotype-guided analyses. Independence between host phenotypes and microbiome types were analyzed by Fisher exact test.
  
  
  RESULTS
  Esophageal microbiomes can be classified into 2 types. The type I microbiome was dominated by the genus Streptococcus and concentrated in the phenotypically normal esophagus. Conversely, the type II microbiome contained a greater proportion of gram-negative anaerobes/microaerophiles and primarily correlated with esophagitis (odds ratio, 15.4) and Barrett's esophagus (odds ratio, 16.5).
  
  
  CONCLUSIONS
  In the human distal esophagus, inflammation and intestinal metaplasia are associated with global alteration of the microbiome. These findings raise the issue of a possible role for dysbiosis in the pathogenesis of reflux-related disorders.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York, USA.
authors.forename: Liying
authors.initials: L
authors.lastname: Yang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lu
authors.forename: Carlos W
authors.initials: CW
authors.lastname: Nossa
authors.forename: Fritz
authors.initials: F
authors.lastname: Francois
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Pei
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001471:Barrett Esophagus / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D001707:Biopsy, Needle; D016022:Case-Control Studies; D016001:Confidence Intervals; D004941:Esophagitis / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D007414:Intestinal Neoplasms / Q000382:microbiology* / Q000473:pathology; D008297:Male; D054892:Metagenome / Q000235:genetics / Q000502:physiology*; D008679:Metaplasia / Q000473:pathology; D008875:Middle Aged; D016017:Odds Ratio; D011230:Precancerous Conditions / Q000473:pathology; D013291:Streptococcus / Q000235:genetics / Q000472:pathogenicity*; D046509:Tissue Culture Techniques