Proton pump inhibitors (PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease (GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls (HCs) using 16S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPI-user and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae, Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on short-term PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.
Adult ; Aged ; Bacteria ; genetics ; isolation & purification ; Feces ; microbiology ; Female ; Gastric Mucosa ; microbiology ; Gastroesophageal Reflux ; drug therapy ; microbiology ; Gastrointestinal Microbiome ; drug effects ; Humans ; Male ; Microbiota ; Middle Aged ; Proton Pump Inhibitors ; therapeutic use ; RNA, Ribosomal, 16S ; genetics

BACKGROUND/AIMS: The acid suppressive effect of omeprazole (OMP) is influenced by the metabolic capacity of gastric acid suppression, which is dependent on CYP2C19 polymorphism. The aim of this study was to determine the influence of CYP2C19 polymorphism and Helicobacter pylori (H. pylori) infection on the intragastric acid suppression of OMP. METHODS: Thirty one patients with gastroesophageal reflux disease were treated with a daily oral dose of 20 mg OMP for 28 days. Patients were genotyped for CYP2C19 polymorphism by polymerase chain reaction-restriction fragment length polymorphism and classified into three groups: homogenous extensive metabolizers (Ho-EMs), heterogenous extensive metabolizers (Ht-EMs) and poor metabolizer (PMs). H. pylori infection status were assessed before OMP treatment. Intragastric pH was monitored over twenty four-hours before (day 0) and after (day 29) the treatment with OMP. RESULTS: Twenty four-hour intragastric mean pH in the PMs group was significantly higher than those in Ho-EMs and Ht-EMs (5.3+/-1.3 vs. 2.8+/-0.6, 3.6+/-1.4) (p<0.005). Twenty four-hour intragastric mean pH after the administration of OMP in the H. pylori positive group was significantly higher than the H. pylori negative group (4.7+/-1.4 vs. 3.2+/-1.4) (p<0.001). There was no significant difference in acid suppressive activity of OMP between H. pylori positive and negative group according to CYP2C19 polymorphism. CONCLUSIONS: The acid suppressive effect of OMP on intragastric pH is dependent on CYP2C19 polymorphism and the H. pylori-infected status in patients with gastroesophageal reflux disease. H. pylori infection may play a role in enhancing the acid suppressive potential of OMP.
Adult ; Aryl Hydrocarbon Hydroxylases/*genetics ; Female ; Gastroesophageal Reflux/*drug therapy/genetics/microbiology ; Genotype ; Helicobacter Infections/*complications ; *Helicobacter pylori/isolation & purification ; Heterozygote ; Homozygote ; Humans ; Hydrogen-Ion Concentration ; Male ; Middle Aged ; Omeprazole/administration & dosage/*therapeutic use ; *Polymorphism, Genetic ; Proton Pump Inhibitors/administration & dosage/*therapeutic use