Long-term proton pump inhibitor therapy leads to small bowel bacterial overgrowth as determined by breath hydrogen and methane excretion

J Breath Res. 2018 Mar 12;12(3):036006. doi: 10.1088/1752-7163/aa9dcf.


Objectives: Prolonged suppression of gastric acid secretion by proton pump inhibitors (PPIs) may alter the bacterial microbiota of the upper gastrointestinal tract and lead to small bowel bacterial overgrowth (SBBO). Published reports have shown conflicting results on the association between PPI therapy and risk of SBBO development. We evaluated whether long-term PPI treatment is associated with presence of SBBO as determined by breath hydrogen (H2) and methane (CH4) excretion. We also assessed the differences in H2/CH4 excretion patterns in patients taking PPI compared with those not taking the medication and searched for the potential predictors of a positive breath test result.

Material and methods: This was a prospective cohort study that included 67 PPI-treated patients (PPIT) and 62 not-receiving PPI (C, comparison). PPIT and C underwent a glucose H2/CH4 breath test (HMBT) to determine the presence of SBBO.

Results: The prevalence of SBBO was significantly higher in PPIT compared to C (44.8% versus 21%, p = 0.005, OR = 3.06, 95% CI 1.40-6.66) as determined by H2 and CH4 excretion. We found that PPIT had all H2 test parameters (baseline H2 levels, maximum peak of H2 as well as mean H2 through the whole test) significantly higher than C. Even those PPIT who did not meet the criteria of breath test positivity had statistically higher breath H2 levels compared to C. Although we did not observe significant differences in CH4 excretion between groups, 19.4% of PPIT and 12.9% of C would have had a false-negative HMBT results had CH4 not been taken into account.

Conclusions: Long-term PPI use was found to be significantly associated with SBBO development as determined by breath H2 and CH4 excretion. CH4 determination reduces the number of falsely negative test results.

MeSH terms

  • Adult
  • Aged
  • Blind Loop Syndrome / diagnosis*
  • Blind Loop Syndrome / etiology*
  • Breath Tests / methods*
  • Female
  • Glucose / analysis
  • Humans
  • Hydrogen / analysis*
  • Intestine, Small / microbiology*
  • Logistic Models
  • Male
  • Methane / analysis*
  • Middle Aged
  • Prospective Studies
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use*
  • Time Factors


  • Proton Pump Inhibitors
  • Hydrogen
  • Glucose
  • Methane