Signatures within the esophageal microbiome are associated with host genetics, age, and diseaseOriginal paper
What was studied?
Researchers assessed the esophageal microbiome of 106 prospectively recruited patients at Prince of Wales Hospital, Sydney, spanning normal esophagus, GERD, glandular mucosa, and Barrett's esophagus. They tested associations between microbiome composition and age, gender, proton pump inhibitor use, host genetics, and disease stage along the esophageal adenocarcinoma cascade.
How was it studied?
The team combined 16S rRNA and 18S rRNA amplicon sequencing with shotgun metagenomic sequencing of esophageal brushings. Host single nucleotide polymorphisms were identified from shotgun reads mapped to the human genome and tested for association with microbiome composition using MicrobiomeGWAS, then validated with custom Fluidigm SNP assays.
What did they find?
The esophageal microbiome clustered into three functionally distinct community types, or esotypes, defined by a consistent co-exclusion relationship between Streptococcus and Prevotella. Age significantly shaped microbiome composition, while Gram-negative oral-associated bacteria and microbial lactic acid production pathways (homolactic and heterolactic fermentation) were enriched in GERD and Barrett's esophagus. Bacteriophages were detected in 97.8 percent of subjects, and low-abundance archaea and Candida species were also present. Three host SNPs, in NOTCH2, STEAP2-AS1, and NREP, were validated as associated with microbiome composition.
Why it matters
This is described as the most comprehensive assessment of the esophageal microbiome to date, linking specific bacterial signatures and host genetic markers to early stages of the esophageal adenocarcinoma cascade. The findings identify candidate targets for further investigation in Barrett's esophagus and esophageal adenocarcinoma development.