Effect of proton pump inhibitors in infants with esophageal atresia on the gut microbiome: a pilot cohort

Abstract

Background The effects of proton-pump inhibitors (PPIs) on the infant microbiome remain unclear. Swedish pilot cohort study to assess the longitudinal effect of long-term PPI on the infant gut microbiome, including ten newborn infants operated for esophageal atresia exposed to PPIs (mean 57 weeks), compared to healthy one-year-old controls. All children were born vaginally and were otherwise healthy. Within- and between sample diversity of the fecal microbiome was assessed using untargeted whole genome Shotgun metagenomics which sequences all the DNA in the sample and can capture genes rather than a taxonomic fingerprint. Results A longer duration of PPI-use was associated with considerable changes in evenness and high variation on diversity within samples compared to a shorter duration of use. The limited difference between baseline samples and controls suggests that this shift was most likely due to the drug exposure and not the underlying alterations on the microbiome. We found no associations with the number of antibiotic treatment episodes among the PPI-users. Conclusion Prolonged PPI-use may alter the early infant gut microbiome composition, especially those with the most prolonged duration of use.

Population-based cohort study: proton pump inhibitor use during pregnancy in Sweden and the risk of maternal and neonatal adverse events

“…In addition, the initial gut colonization is highly influenced by the maternal microbiome (vaginal and fecal) [6,7], and the maternal microbiome seems to play an important role in the onset of pregnancy complications [8][9][10]. In turn, PPI use has been associated with important changes in the gut microbiome that appear to be more prominent than those related to antibiotic use [11], also in infants as shown in our small pilot study [12]. The Food and Drug Administration (FDA) used to classify (up till 2015) most PPIs as category B drugs ("No risk in animal studies"), except for omeprazole which was categorized as type C ("Risk cannot be ruled out") [13,14].…”

“…To our knowledge, there are no randomized clinical trials investigating the safety of maternal PPI use, regarding maternal and neonatal adverse events [2,45,46]. We also question if it is still ethically defendable to conduct these on PPI use during pregnancy with the accumulating safety concerns based on association studies, and our increasing understanding of drug interactions and the microbiome [2,5,12,47,48].…”

Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

“…24 Similarly, prolonged PPI use in infants is associated with changes in the evenness and diversity of bacteria. 25 Acid suppressants have also been demonstrated to increase sensitization to orally digested proteins. 26 In a recent meta-analysis, 10 childhood acid suppressant use has been associated with elevated risk of asthma, atopic dermatitis, and allergic rhinitis.…”

“…In an assessment before and after PPI treatment of the fecal microbiome, the relative abundance of Lactobillus and Stentrophomonas species decreased with PPI treatment . Similarly, prolonged PPI use in infants is associated with changes in the evenness and diversity of bacteria . Acid suppressants have also been demonstrated to increase sensitization to orally digested proteins .…”

Intestinal dysbiosis and inflammation in children with repaired esophageal atresia

“…23 In a recent pilot study assessing the effect of PPI's on infants with EA, it was shown that longer duration of PPI use was associated with lower Shannon diversity. 24 Children with EA had a significant difference in bacterial communities compared to HC based on beta diversity analysis. In the current study, the order Lactobacillales was enriched in children with EA compared to HC.…”