The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial

Summary Background & Aims Probiotics contain living microorganisms consumed for their putative benefits on the intestinal microbiota and general health and a concept is emerging to use probiotic as a therapeutic intervention to reduce proton pump inhibitors (PPIs) negative effects, but data is lacking. The use of PPIs can result in disordered gut microbiota, leading to a risk of enteric infections. PPIs are frequently prescribed in the general practice setting for gastroesophageal reflux disease (GERD), peptic ulcer disease, and related conditions. Despite the availability and widespread use of probiotics and acid-suppressing medications, the effect of PPIs-induced gastric acid suppression on the survival and colonization of probiotics bacterial species is currently unclear. We hypothesized that gastric acid suppression may improve intestinal colonization of probiotics bacterial species and probiotic intervention may have a potential role in mitigating untoward effects of PPI. Methods In a randomized, double-blind, placebo-controlled study, healthy subjects were given either proton pump inhibitor (PPI, n=15) or placebo (n=15) over 6 weeks. All subjects then consumed multi-strain probiotics from weeks 2 to 6. Thirty participants (10 males, 20 females, age range: 18-56 years) were enrolled in the study. Shotgun metagenomic sequencing and untargeted metabolomics analyses were performed on stool samples collected at week 0, 2, and 6. Results Short term PPI treatment increased the microbial abundance of Streptococcaceae (p=0.004), Leuconostacaceae (p =0.001), and Pasteurellaceae (p =0.020) at family level and corresponding genus levels. The metabolomic analysis of the stools revealed a change in 10 metabolites where Gly Arg Val and phenylacetic acid were consistently increased compared to the baseline. Probiotic intervention inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p =0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. Notably, PPI enhanced the colonization of certain probiotic bacterial species like Streptococcus thermophilus (p Conclusion Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations. ( ClinicalTrials.gov , number NCT03327051).