Vanderbilt University Medical Center Nashville, TN
Introduction: Proton-pump inhibitors (PPIs) are empirically used to treat children with esophageal symptoms even when there are no histologic abnormalities (normal esophagus). Little is known about the impact of PPIs on the molecular profile and microbiome of a normal pediatric esophagus. Our aim was to investigate the effects of PPIs on esophageal epithelial transcriptional and active microbiota responses in children with a normal esophagus. We hypothesized that the PPIs alter the epithelial transcriptional profile and active esophageal microbiome simultaneously in children with normal esophagus.
Methods: Distal esophageal biopsies obtained from 20 children (6-18 years) with esophageal symptoms and without any histologic abnormalities were included in the analysis. Seven children were not on a PPI (PPI-) and 13 were on a PPI (PPI+). They were not on any concurrent medications or antibiotics. Metatranscriptomic methods were used to capture host transcriptional and microbial profiles from the biopsies. Transcripts mapped to the human genome were used for gene expression analysis. Microbial transcripts were used to profile active microbial abundance, alpha diversity and beta diversity.
Results: The median (IQR) age of the cohort was 14 (12-15) years. Compared to PPI-, the PPI+ children showed upregulation of 19 genes and no genes were downregulated (Fig 1A). The prominent mucin genes (MUC2 and MUC3), DMBT1 (deleted in malignant brain tumor 1) - a regulator of mucosal homeostasis possibly through the linking of mucosal defense and regeneration, FABP1 (Fatty Acid-Binding Protein 1) involved in the binding, transport and metabolism of long-chain fatty acids, and Trefoil factor 3 (TFF3) involved in the maintenance and repair of the intestinal mucosa were upregulated. Microbial transcripts revealed Haemophilus sp. Lawsonella sp. and Propionibacterium sp. were significantly abundant in PPI-, whereas Prevotella sp. and Streptococcus sp. were highly abundant in PPI+ (Fig. 1B). There was no differences in the alpha and beta diversity between the two groups (Fig 1C).
Discussion: Metatranscriptomic analysis of normal pediatric esophageal samples revealed that PPIs increase the expression of genes involved in esophageal epithelial cell function and mucosal homeostasis, and also leads to alterations in the esophageal microbiome simultaneously. Studies are underway to confirm our results in a larger group of children.
