Gastrointestinal microbiota alterations associated with pediatric gastroesophageal reflux disease and proton pump inhibitor exposure: a systematic review of microbiome changes, dysbiosis markers, and associated clinical outcomes
Abstract
Introduction: Gastroesophageal reflux disease (GERD) and proton pump inhibitor (PPI) therapy have both been associated with alterations of the developing gastrointestinal microbiome and potential downstream clinical consequences in children. However, available evidence is fragmented across disease-related, treatment-related, and mechanistic studies, making the overall biological relationship difficult to interpret.
Methods: PubMed, Web of Science, and Scopus databases were queried for the period January 2000 to May 2026 to synthesize evidence across the pathophysiological continuum linking pediatric GERD, microbiota alterations, inflammatory mechanisms, PPI exposure, and microbiota-associated clinical outcomes.
Results: The review included studies evaluating children with GERD as well as mechanistic studies involving pediatric upper gastrointestinal conditions requiring PPI therapy when microbiota-related outcomes were relevant to the review objective. Study selection was performed according to PRISMA guidelines, 31 of which were included in the final analysis. The data indicate that pediatric exposure to GERD and PPI is associated with changes in the gastrointestinal microbiota at multiple levels (oral, esophageal, gastric, and intestinal). These changes include reduced microbial diversity, changes in bacterial composition (particularly Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria), and increased similarity of microbiota between aerodigestive compartments,…
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Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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