The proton pump inhibitor omeprazole does not promote Clostridioides difficile colonization in a murine model

Abstract

Proton pump inhibitor (PPI) use has been associated with microbiota alterations and susceptibility to Clostridioides difficile infections (CDIs) in humans. We assessed how PPI treatment alters the fecal microbiota and whether treatment promotes CDIs in a mouse model. Mice receiving a PPI treatment were gavaged with 40 mg/kg of omeprazole during a 7-day pretreatment phase, the day of C. difficile challenge, and the following 9 days. We found that mice treated with omeprazole were not colonized by C. difficile. When omeprazole treatment was combined with a single clindamycin treatment, one cage of mice remained resistant to C. difficile colonization, while the other cage was colonized. Treating mice with only clindamycin followed by challenge resulted in C. difficile colonization. 16S rRNA gene sequencing analysis revealed that omeprazole had minimal impact on the structure of the murine microbiota throughout the 16 days of omeprazole exposure. These results suggest omeprazole treatment alone is not sufficient to disrupt microbiota resistance to C. difficile infection in mice that are normally resistant in the absence of antibiotic treatment.