Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome

Abstract

OBJECTIVE Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. METHODS Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI−], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. RESULTS The median (IQR) age of our cohort was 14 years (12–16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI−, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI− and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. CONCLUSIONS In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.