July 2012 E-Journal Club


Summer in C’ville has been somewhat eventful thus far, with a recent windstorm in the middle of a heat wave that uprooted trees and knocked out the electricity for a few days.  Summer is also when our new residents and fellows arrive starting a whole new cycle of rotations, lectures and questions.

Our journal club this month deals with proton pump inhibitor medications which have been increasingly scrutinized over the last several years with possible links to pneumonia, clostridium difficile and bacterial overgrowth incidence, among other concerns.

July Citation:

Ratuapli SK, Taylor G. Ellington TG, O ’ Neill MT, et al.  Proton Pump Inhibitor Therapy Use Does Not Predispose to Small Intestinal Bacterial Overgrowth.  Am J Gastroenterol 2012; 107:730–735.


This was a retrospective study designed to investigate if proton pump inhibitor medications (PPIs) increase the incidence of small intestine bacterial overgrowth (SIBO) as diagnosed by glucose hydrogen breath testing (GHBT).  Electronic medical records of 1191 patients that had completed a GHBT between 2004 – 2010 were retrospectively reviewed to compare the prevalence of SIBO in patients on PPI therapy compared with those not on PPI therapy. In addition, the investigators also recorded differences in the proportion of positive GHBT between patients on PPI once vs. twice daily and evaluated potential factors that might predict GHBT positivity.

Inclusion and Exclusion Criteria were:

Inclusion criteria:

Patients at the Mayo clinic in Arizona who completed a GHBT between 2004 – 2010.

Exclusion criteria:

History of prior GI surgery (except chole, appe, hysterectomy, or pelvic floor surgery) those on antibiotics or having completed a bowel preparation for colonoscopy or other bowel cleansing within the previous 30 days.

Major Results reported by authors:

No significant differences were found in:

  • Proportion of patients testing positive for SIBO between PPI users and PPI nonusers based on the 4 criteria for a positive H2 breath test.
  • Subgroup analysis evaluating the influence of PPI dose frequency on the proportion of patients with a positive breath test between once daily vs. twice daily PPI use.
  • Those patients on once daily PPIs that had a positive GHBT was numerically (but not significantly) higher than that of patients on twice daily PPIs.

Author’s Conclusions:

  • PPI use was not associated with SIBO based on GHBT
  • Differences in sample size, pt characteristics, geographic location, dietary intake, and test used to diagnose SIBO might explain the observed variation in results from other studies.
  • Further prospective studies are needed to confirm these findings.


The strengths of this study include the large number of patients included, and the fact that the investigators evaluated 4 different commonly used criteria to evaluate GHBT positivity.

As this was an observational study, and patients were not randomized to receive PPI’s, some of the same factors that led to patients being prescribed a PPI (or not) may have also influenced development of SIBO.  In an observational study there is just no way to statistically control for all of the factors that might influence development of SIBO, for instance, in this study there was no accounting (or control for) collagen vascular diseases, chronic pancreatitis, and liver disease.

Another limitation that the group discussed was that there was no way to know how long patients had been receiving a PPI, nor how compliant patients were with their medications.  Considering that it was a retrospective study, and knowing how notoriously inaccurate electronic medical records are in regards to the “current medication” list for outpatients1, there is no way to know for sure how many of the “PPI group” was really taking PPIs, nor how many of the non-users were actually taking them.

The GHBT used glucose as a substrate, and we know that glucose is rapidly absorbed in the proximal small bowel, so that the test used for the study would not reflect SIBO in the more distal bowel, and may not be consistent with the results of other breath testing or duodenal aspirates.  Furthermore, up to 27% of patients do not produce hydrogen.

Our Take Home Message (s)

  1. The results of studies investigating SIBO risk associated with PPIs have not been consistent.  There is a need for a large randomized study to determine if the use of PPIs will increase the likelihood of SIBO, especially in high risk patients.
  2. Regardless of SIBO incidence there are indications that PPIs should be used with discretion relating to cost, incidence of clostridium difficile infections and nutrient (Fe, Ca) absorption.



  1. Toll E. The Cost of Technology. JAMA. 2012;307(23):2497-2498.


Other News on the UVAHS GI Nutrition Website: (www.ginutrition.virginia.edu):

Upcoming Webinars for Spring 2012:

–Tuesday, September 11:  A Practical Approach to Hydration–Carol Rees Parrish, MS, RD

–Tuesday, October 23:  Growing Power for Preterm and High Risk Infants–Patti Perks, MS, RD

–Tuesday, November 13:  Nutritional Anabolics–Joe Krenitsky, MS, RD

–Tuesday, December 11—TBA


Check out What’s New:

–“ Resources for the Nutrition Support Clinician

Latest Practical Gastroenterology article:

–Naik AS, Venu N.  Nutritional Care in Adult Inflammatory Bowel Disease.  Practical Gastroenterology 2012;XXXVI(6):18.

–Frank Van der Aa F, De Ridder D, Van Poppel H. When the Bowel Becomes The Bladder: Changes In Metabolism After Urinary Diversion.  Practical Gastroenterology 2012;XXXVI(7):15.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD

PS – Please feel free to forward on to friends and colleagues.