Abstract
Proton pump inhibitors (PPIs) are the standard therapy for gastroesophageal reflux disease. In adults, PPI treatment is associated with Clostridium difficile infections (CDI). In contrast to adults the microbiome of infants develops from sterility at birth toward an adult-like profile in the first years of life. The effect of PPIs on this developing microbiome has never been studied. The aim of the present study was to determine the effect of oral PPIs on the fecal microbiome in infants with gastroesophageal reflux disease (GERD). In this prospective longitudinal study 12 infants with proven GERD received oral PPIs for a mean period of 18 weeks (range 8–44). Stool samples were collected before (“before PPI”) and 4 weeks after initiation of PPI therapy (“on PPI”). A third sample was obtained 4 weeks after PPI discontinuation (“after PPI”). The fecal microbiome was determined by NGS based 16S rDNA sequencing. This trial was registered with clinicaltrials.gov (NCT02359604). In a comparison of “before PPI” and “on PPI” neither α- nor β-diversity changed significantly. On the genus level, however, the relative abundances showed a decrease of Lactobacillus and Stenotrophomonas and an increase of Haemophilus. After PPI therapy there was a significant increase of α- and β-diversity. Additionally, the relative abundances of the phyla Firmicutes, Bacteroidetes, and Proteobacteria were significantly changed and correlated to patients' age and the introduction of solid foods. PPI treatment has only minor effects on the fecal microbiome. After discontinuation of PPI treatment the fecal microbiome correlated to patients' age and nutrition.
Highlights
Gastroesophageal reflux (GER) is a common finding in infants caused by temporary relaxations of the immature lower esophageal sphincter (LES) (Vandenplas et al, 2007)
In contrast to most studies reported in adults gastroesophageal reflux disease (GERD) was suspected in our patients, but proven by impedance monitoring prior to enrollment and pump inhibitors (PPIs) therapy
Up to now the majority of studies investigating the effect of PPI on gut microbiota have compared adult PPI users to nonusers
Summary
Gastroesophageal reflux (GER) is a common finding in infants caused by temporary relaxations of the immature lower esophageal sphincter (LES) (Vandenplas et al, 2007). May develop gastroesophageal reflux disease (GERD) associated with vomiting, feeding problems, pain, esophagitis, failure to thrive and/or recurrent respiratory infections (Rudolph et al, 2001; Colletti and Di Lorenzo, 2003). In these infants conservative therapy includes upright positioning, increased feeding frequencies with lower amounts and food thickeners (Hollwarth, 2012). Possible side effects of prolonged PPI therapy include an increased risk of community acquired enteritis and Clostridium difficile infections (CDI) (Janarthanan et al, 2012; Bouwknegt et al, 2014; McDonald et al, 2015)
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