Large Study Fails to Link PPI Therapy to Small Intestinal Bacterial Overgrowth

February 27, 2012

By Megan Brooks

NEW YORK (Reuters Health) Feb 24 - Contrary to current thinking, a new study suggests that proton pump inhibitors (PPIs) do not predispose to small intestinal bacterial overgrowth (SIBO).

"The study was prompted by reports suggesting an association between PPI use and the development of SIBO," Dr. Michael Crowell of the Mayo Clinic, Scottsdale, Arizona, told Reuters Health by email.

"In our very busy motility laboratories, we test a substantial number of patients for SIBO - many are on PPIs. From my clinical observations, there did not appear to be any association between PPI use and SIBO positive breath tests. Therefore, we decided to test our hypothesis that there was no significant association using our database."

Altogether, Dr. Crowell and his colleagues looked at data on 1,191 patients (70% women) who had glucose hydrogen breath testing (GHBT) from 2004 to 2010. Slightly less than half -- 556 patients, or 48% -- were PPI users.

In all subjects, breath samples for hydrogen (H2) and methane (CH4) were collected before, and every 20 minutes for 120 minutes, following ingestion of a 50-g oral glucose load.

The following criteria were used to define a positive GHBT: an increase in H2 greater than 20 parts per million (ppm) over baseline; a sustained increase in H2 greater than 10 ppm over baseline; CH4 greater than 15 ppm over baseline; and either an increase in H2 greater than 20 ppm over baseline or CH4 greater than 15 ppm.

In support of the team's hypothesis, they didn't find any differences in rates of abnormal breath tests between patients on or off PPI therapy. PPI use was not significantly associated with GHBT positivity.

In a paper online February 14 in the American Journal of Gastroenterology, they further report that subgroup analysis to evaluate the influence of PPI dose frequency on the proportion of patients with a positive breath test showed no significant differences between once daily vs twice daily PPI use based on any of the four criteria evaluated.

"Importantly," they say the lack of association between PPI use and GHBT remained strong after adjusting for potential confounding factors such as age, body mass index, diabetes, irritable bowel syndrome, and laxative/antidiarrheal use.

"Owing to the widespread use of PPIs and an increasing interest in the role of SIBO in a variety of conditions, the association of SIBO with PPI use has recently generated significant clinical interest," the authors note.

"The take-home message," Dr. Crowell said, "is that the probability that PPI use increases the risk of developing SIBO appears to be quite small in our clinic population."

In the past 10 years, studies using different tests for detecting SIBO have addressed the association between SIBO and PPI use and have yielded conflicting findings. "This means that it is quite likely that other factors may also influence GHBT positivity," the authors say.

"For example," they add, "it is easy to speculate that differences in diet might affect the study results. The majority of the studies suggesting a positive association between PPI use and SIBO were conducted in Europe, while the studies suggesting a negative association were from the United States raising the hypothesis that differences in dietary factors in different geographical location might affect the study results."

The conflicting study results may also stem, at least in part, from the lack of a true gold standard test to diagnose SIBO, the authors say.

The chief limitation of the study is the retrospective design, with its inherent issues of confounding, the authors admit, although they tried to control for potential confounding factors.

They also note that duration of PPI therapy may be associated with the probability of a positive GHBT, information that was not included in the analysis. However, they say in their tertiary care center most patients taking PPIs were on chronic acid suppression therapy that would be expected to increase the potential for an abnormal GHBT, rather than reduce the likelihood of GHBT positivity.

Strengths of the study include its large (adequately powered) size and use of multiple criteria to evaluate for breath test positivity, they say.

The study had no outside financial support and the authors have declared no potential competing interests.


Am J Gastroenterol 2012.