Rachel Rosen1, Lan Hu2, Janine Amirault3, Umakanth Khatwa4, Doyle V Ward5, Andrew Onderdonk6. 1. Aerodigestive Center, Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA. Electronic address: rachel.rosen@childrens.harvard.edu. 2. Center for Computational Cancer Biology, Dana Farber Cancer Institute, Boston, MA. 3. Aerodigestive Center, Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA. 4. Aerodigestive Center, Division of Pulmonary Medicine, Boston Children's Hospital, Boston, MA. 5. The Broad Institute, Cambridge, MA. 6. Department of Microbiology, Brigham and Women's Hospital, Boston, MA.
Abstract
OBJECTIVES: To test the hypothesis that proton pump inhibitor (PPI) use results in changes in gastric microflora which, through full column reflux, results in lung and oropharyngeal microflora changes. STUDY DESIGN: We performed a prospective, cross-sectional cohort study of 116 children (57 off and 59 on PPIs) undergoing simultaneous bronchoscopy and upper endoscopy for the evaluation of chronic cough. We performed 16S sequencing on gastric, bronchoalveolar lavage, and oropharyngeal fluid. Fifty patients also underwent multichannel intraluminal impedance testing. RESULTS: Streptococcus was more abundant in the gastric fluid of patients taking PPIs, and there was a significant correlation with PPI dose (mg/kg/d) and abundance of gastric Streptococcus (P = .01). There was also a significant difference in the abundance of oropharyngeal Streptococcus in patients treated with PPI. Eight unique bacterial genera were found in the gastric and lung fluid but not in the oropharyngeal suggesting exchange between the 2 sites and 2 of the 8 (Lactococcus, Acinetobacter) were more abundant in patients with more full column reflux, suggesting direct aspiration. Principal component analysis revealed greater overlap between gastric and lung than oropharyngeal microflora. CONCLUSIONS: PPI use was associated with differences in gastric, lung, and oropharyngeal microflora. Although microflora exchange can occur between all 3 sites, gastric and lung microflora are more closely related, and the mechanism of exchange between sites may be aspiration of full column reflux.
OBJECTIVES: To test the hypothesis that proton pump inhibitor (PPI) use results in changes in gastric microflora which, through full column reflux, results in lung and oropharyngeal microflora changes. STUDY DESIGN: We performed a prospective, cross-sectional cohort study of 116 children (57 off and 59 on PPIs) undergoing simultaneous bronchoscopy and upper endoscopy for the evaluation of chronic cough. We performed 16S sequencing on gastric, bronchoalveolar lavage, and oropharyngeal fluid. Fifty patients also underwent multichannel intraluminal impedance testing. RESULTS: Streptococcus was more abundant in the gastric fluid of patients taking PPIs, and there was a significant correlation with PPI dose (mg/kg/d) and abundance of gastric Streptococcus (P = .01). There was also a significant difference in the abundance of oropharyngeal Streptococcus in patients treated with PPI. Eight unique bacterial genera were found in the gastric and lung fluid but not in the oropharyngeal suggesting exchange between the 2 sites and 2 of the 8 (Lactococcus, Acinetobacter) were more abundant in patients with more full column reflux, suggesting direct aspiration. Principal component analysis revealed greater overlap between gastric and lung than oropharyngeal microflora. CONCLUSIONS: PPI use was associated with differences in gastric, lung, and oropharyngeal microflora. Although microflora exchange can occur between all 3 sites, gastric and lung microflora are more closely related, and the mechanism of exchange between sites may be aspiration of full column reflux.
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