Computational Comparative Analysis of Esophageal Microbial Communities and Metabolic Profiles in Erosive and Nonerosive Phenotypes of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) manifests in distinct phenotypes, including erosive reflux disease (ERD) and nonerosive reflux disease (NERD), which exhibit differences in pathophysiology and clinical outcomes. This study aims to explore microbial differences across these phenotypes. RNA sequencing data of 69 esophageal samples from reflux esophagitis (RE) and NERD patients were retrieved from NCBI SRA to identify key microbial taxa. Alpha and beta diversity analyses were conducted, and DESeq2 and Lefse analyses were used to identify bacterial biomarkers to differentiate ER from NERD. Five dominant phyla were identified’ namely, Actinomycetota, Bacillota, Fusobacteriota, Pseudomonadota and Thermodesulfobacteriota. Genera such as Streptococcus, Fusobacterium and Phyllobacterium were abundant across the samples. Alpha diversity analysis revealed significant differences at the phylum, genus and species levels, with notable findings for Shannon, Chao1 and Simpson indices. Beta diversity analysis revealed significant differences in the microbial composition between ER and NERD at all taxonomic levels ([Formula: see text] < 0.001). DESeq2 analysis identified four phyla, 13 genera and 12 species with differential abundances between ER and NERD. Thermodesulfobacteriota and Actinomycetota were more abundant in NERD, whereas Pseudomonadota and Bacteroidota were higher in ER. At the species level, Acinetobacter baumannii and Escherichia coli were enriched in NERD, whereas Streptococcus mitis and Pseudoxanthomonas mexicana were elevated in ER. Lefse analysis identified potential bacterial biomarkers, with Thermodesulfobacteriota and Desulfomicrobium being significantly associated with NERD, whereas Fusobacteriota was linked to ER. Significant microbial differences were observed between ER and NERD, with distinct bacterial biomarkers identified. These findings suggest that the esophageal microbiota may play a role in the pathogenesis of reflux diseases, offering potential diagnostic and therapeutic targets. Further clinical research is needed to confirm these results and explore their clinical implications.