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. 2019 Oct;28(10):1687-1693.
doi: 10.1158/1055-9965.EPI-19-0008. Epub 2019 Aug 29.

Alterations to the Esophageal Microbiome Associated With Progression From Barrett's Esophagus to Esophageal Adenocarcinoma

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Alterations to the Esophageal Microbiome Associated With Progression From Barrett's Esophagus to Esophageal Adenocarcinoma

Erik J Snider et al. Cancer Epidemiol Biomarkers Prev. .
Free PMC article


Background: The incidence of esophageal adenocarcinoma has risen dramatically over the past half century, and the underlying reasons are incompletely understood. Broad shifts to the upper gastrointestinal microbiome may be partly responsible. The goal of this study was to describe alterations in the esophageal microbiome that occur with progression from Barrett's esophagus to esophageal adenocarcinoma.

Methods: A case-control study was performed of patients with and without Barrett's esophagus who were scheduled to undergo upper endoscopy. Demographic, clinical, and dietary intake data were collected, and esophageal brushings were collected during the endoscopy. 16S rRNA gene sequencing was performed to characterize the microbiome.

Results: A total of 45 patients were enrolled and included in the analyses [16 controls; 14 Barrett's esophagus without dysplasia (NDBE); 6 low-grade dysplasia (LGD); 5 high-grade dysplasia (HGD); and 4 esophageal adenocarcinoma]. There was no difference in alpha diversity between non-Barrett's esophagus and Barrett's esophagus, but there was evidence of decreased diversity in patients with esophageal adenocarcinoma as assessed by Simpson index. There was an apparent shift in composition at the transition from LGD to HGD, and patients with HGD and esophageal adenocarcinoma had decreased Firmicutes and increased Proteobacteria. In addition, patients with HGD or esophageal adenocarcinoma had increased Enterobacteriaceae and Akkermansia muciniphila and reduced Veillonella. In the study population, patients taking proton pump inhibitors had increased Streptococcus and decreased Gram-negative bacteria overall.

Conclusions: Shifts in the Barrett's esophagus-associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria.

Impact: The microbiome may play a role in esophageal carcinogenesis.

Conflict of interest statement

Conflicts of Interest: The authors declare no potential conflicts of interest.


Figure 1.
Figure 1.
Relative abundance of the major phyla comparing subjects with no dysplasia or LGD to those with HGD or EAC. Compared to NDBE/LGD subjects, those with HGD or EAC had decreased Firmicutes (p=0.04) and increased Proteobacteria (p=0.04).
Figure 2.
Figure 2.
(A) Cladogram from LEfSe analyses of differentially abundant taxa comparing BE patients without dysplasia (NDBE) or LGD vs. HGD or EAC. (B) Subjects with HGD or EAC had reduced relative abundance of Veillonalla (left), and had increased proportion of samples with presence of the other differentially abundant taxa (right), which were relatively rare. (Presence defined as having any reads, except for Enterobacteriaceae, which was defined as relative abundance >0.1%.)
Figure 3.
Figure 3.
Compared to controls not taking PPIs, patients taking PPIs had: (A) reduced relative abundance of Gram-negative bacteria (p=0.05), and (B) increased relative abundance of Streptococcus (p=0.03).

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