Gastrointestinal tract bacteriomes in patients with gastroesophageal reflux disease: a multicenter study

Background and Aims: Gastroesophageal reflux disease (GERD) and its complications–reflux esophagitis (RE), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC)–have been associated with bacterial dysbiosis. However, comprehensive characterization of the gastrointestinal tract (GIT) bacteriome across these GERD complications is lacking. This multicenter observational study aimed to fill this gap and evaluate the possibility of identifying non-invasive oral or rectal biomarkers for advanced GERD complications. Methods: Biopsies from patient-matched pathological esophageal tissues, gastric body and antrum, duodenum, and oral and rectal swabs were collected from 158 patients with histologically confirmed RE, BE, or EAC. DNA isolates were analyzed by qPCR and 16S rRNA amplicon sequencing. Anaerobes/aerobes and gramnegative/grampositive ratios, as well as relative abundances of multiple genera, were compared among GIT sites and study groups. Results: Bacterial load, richness, and evenness in esophageal biopsies increased with the severity of GERD complications. The relative abundance of the commensal genus Streptococcus was significantly higher in esophageal samples of RE than in BE and EAC ( P  = .037 and P  = .017, respectively). Interestingly, BE samples showed distinct bacteriome features deviating from the RE–EAC progression trend. Strong inter-site correlations were identified throughout the GIT bacteriomes. Relative abundances of the genus Porphyromonas ( P  = .034) and other gramnegative periodontal pathogens in oral swabs and a probiotic genus Faecalibacterium in rectal swabs were associated with EAC ( P  = .019). Conclusions: Comprehensive GIT profiling of 923 samples revealed significant bacteriome alterations associated with the GERD complications severity. Some bacterial genera showed promise for potential use as non-invasive biomarkers for predicting the risk of severe GERD complications.