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Objectives: Proton pump inhibitors (PPI) used to suppress acid secretion in the stomach are among the most widely prescribed medications. There is emerging evidence of proton secretion elsewhere in the aerodigestive tract, and acidic microenvironments are integral to oral flora such as Lactobacillus. The hypothesis of this study is that the growth rate and morphology of oral Lactobacillus strains are effected by PPIs. Methods: Nineteen different strains of Lactobacilli were inoculated in microtiter plates at pH of 4.5 to 6.5 and exposed to twofold dilutions of pantoprazole at a range of 2.5 mg/mL to 2.5 μg/mL. Bacterial growth was monitored, and the minimum inhibitory concentration (MIC) of the drug was determined for the strains most sensitive to pantoprazole. Results: In the unexposed (control) group, nine Lactobacilli strains were affected by pH changes from 6.5 to 4.5. In the group exposed to pantoprazole, 9 of the 19 Lactobacilli strains were found to have an MIC below 625 μg/mL, with L. plantarum 14917 being the most sensitive (MIC = 20 μg/mL). In some strains, such as L. s. salivarius 11741, Gram-staining revealed conformational changes in the bacteria when grown in the presence of pantoprazole. Conclusion: Growth rates and morphology of oral Lactobacillus are affected by the pH of the environment. Pantoprazole at supraphysiologic doses further affects growth rates and conformation in some strains. Significance: The balance of oral flora and upper digestive tract homeostasis may be affected by unexpected targets of PPI pharmacotherapy, with possible unanticipated consequences.