title: Bacterial Composition of the Human Upper Gastrointestinal Tract Microbiome Is Dynamic and Associated with Genomic Instability in a Barrett's Esophagus Cohort.
abstract: BACKGROUND
  The incidence of esophageal adenocarcinoma (EAC) has increased nearly five-fold over the last four decades in the United States. Barrett's esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear.
  
  
  METHODS
  The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12) of the Seattle Barrett's Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett's esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this cohort.
  
  
  RESULTS
  Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett's esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett's esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC.
authors.affiliation: Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington, United States of America; Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Alevtina
authors.initials: A
authors.lastname: Gall
authors.affiliation: Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Jutta
authors.initials: J
authors.lastname: Fero
authors.affiliation: Divisions of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Connor
authors.initials: C
authors.lastname: McCoy
authors.affiliation: Divisions of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Claywell
authors.affiliation: Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Carissa A
authors.initials: CA
authors.lastname: Sanchez
authors.affiliation: Divisions of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Blount
authors.affiliation: Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Divisions of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Divisions of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.affiliation: Divisions of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Matsen
authors.affiliation: Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Divisions of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
authors.affiliation: Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Nina R
authors.initials: NR
authors.lastname: Salama
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology; D000368:Aged; D000369:Aged, 80 and over; D001419:Bacteria / Q000145:classification / Q000235:genetics; D001471:Barrett Esophagus / Q000150:complications / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D044822:Biodiversity; D004198:Disease Susceptibility; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D015994:Incidence; D008297:Male; D054892:Metagenome; D064307:Microbiota; D008871:Microvilli / Q000382:microbiology; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D010802:Phylogeny; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D013270:Stomach / Q000382:microbiology; D041742:Upper Gastrointestinal Tract / Q000382:microbiology*; D049629:Waist-Hip Ratio