The Influence of Proton Pump Inhibitors on the Fecal Microbiome of Infants with Gastroesophageal Reflux-A Prospective Longitudinal Interventional Study

Christoph Castellani, Georg Singer, Karl Kashofer, Andrea Huber-Zeyringer, Christina Flucher, Margarita Kaiser, Holger Till, Christoph Castellani, Georg Singer, Karl Kashofer, Andrea Huber-Zeyringer, Christina Flucher, Margarita Kaiser, Holger Till

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.

Keywords: Clostridium difficile; GERD; infants; microbiome; proton pump inhibitors.

Figures

Figure 1
Figure 1
α-diversities (Chao1 index at 12,000 reads) at the three time points tested (n = 12 per time point). In the within-individual comparison there was no statistically significant difference after 4 weeks of PPI treatment (p = 0.729). Four weeks after discontinuation of PPI therapy α-diversities were significantly increased (p = 0.003 for “after PPI” vs. “before PPI” and “on PPI.” Lines connect individuals.
Figure 2
Figure 2
Mean taxa summary plots at the phylum (left panel) and class (right panel) level at the three different time points measured (n = 12 per time point).
Figure 3
Figure 3
Relative abundances of Streptococcus, Enterococcus and Clostridiaceae at the three different time points tested (n = 12 per time point).

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