PPI Use Does Not Lead to Bacterial Overgrowth

Mark Pimentel, MD

Proton pump inhibitor (PPI) use does not lead to bacterial overgrowth in the small intestine, according to a paper published in Digestive Diseases and Sciences.

Investigators from Cedars-Sinai Medical Center conducted microbiome sequencing and culture from 177 patients as part of the REIMAGINE study in order to compare duodenal and stool microbiomes in those who use and do not use PPI.

The patients were aged 18-58 years and underwent upper gastrointestinal endoscopy or double balloon enteroscopy without colonoscopy as part of their standard of care. The participants completed a questionnaire – which covered topics such as demographics, medical history, gastrointestinal symptoms, and medication use – provided a blood sample, and provided an optional stool sample.

While there is some off-label and over-the-counter use of PPI, the study authors wrote, they are among the most widely prescribed medications in some adult populations. Because PPI use decreases gastric acid secretion, it has been suggested that PPI use could lead to increased risks of Clostridium difficile (C diff) infection, as well as small intestinal bacterial overgrowth (SIBO).

SIBO is usually associated with gastrointestinal symptoms such as bloating, excessive gas, abdominal discomfort, diarrhea, and weight loss. SIBO can also be common among diseases such as irritable bowel syndrome, fatty liver, inflammatory bowel disease, diabetic gastroparesis, and Celiac.

Of the total number of patients enrolled in the study, 59 subjects were on PPI at the time of endoscopy and 118 controls were not. The types of PPI being taken by subjects in the cohort using them included omeprazole (27 patients), pantoprazole (23 patients), esomeprazole (6 patients), and others (2 patients).

There were no phylum-level differences between patients that used PPI and those that did not, the study authors said, after evaluating the duodenal microbiome. However, the PPI users showed significantly higher relative abundances of the families Campylobacteraceae (3.13-fold) and Bifidobacteriaceae (2.9-fold), the study authors learned. There was lower relative abundance of Clostridiaceae (88.24-fold) in PPI subjects compared to the non-users, the investigators found.

“We know that PPI increase the risk of C diff,” corresponding author Mark Pimentel, MD, told HCPLive®. “Perhaps the reduction of normal commensal Clostridiacaea leaves the door open for bad actors/squatters such as C diff. This requires further study.”

SIBO rates were not significantly different between the groups, the study authors said, which was true when using cultures or 16S sequencing. It also remained true among PPI subjects taking different PPIs.

The stool microbiome analysis exhibited significantly higher abundance of family Streptococcaceae (2.14-fold) and lower Clostridiaceae (2.60-fold) in PPI patients when compared to non-PPI subjects, the study authors added.

“This is the first trial showing that PPI does not lead to bacterial overgrowth using the best technology available (microbiome sequencing and culture),” Pimentel added. “This paper in some ways settles the matter, but as in all science, needs duplication by other groups.”

He noted that their findings should assuage concerns about SIBO when prescribing treatment with PPI.

“Modest changes were seen in the small intestinal microbiome in PPI users, including a notable reduction in relative abundance of the family Clostridiaceae,” the study authors concluded. “Reduction in the relative abundance of Clostridiaceae was also seen in the stool microbiome, as well as an increase in relative abundance of Streptococcaceae. Based on these results, the overall effects of PPI use on the microbiome appear to be modest, although the clinical importance of these findings is as yet unknown.”