Association between chronic use of proton pump inhibitors and small- intestinal bacterial overgrowth assessed using lactulose hydrogen breath tests

Hepatogastroenterology. Mar-Apr 2015;62(138):268-72.


Background/aims: Several adverse events have been reported in patients who are chronic users of proton pump inhibitors (PPIs); however, the association between PPI use and small-intestinal bacterial overgrowth (SIBO) is controversial. We examined the prevalence of SIBO, as assessed by the lactulose hydrogen breath test (LHBT), based on the use of gastric acid-suppressive drugs in Japanese patients. METH- ODOLOGY: Ninety-four patients who were examined by the LHBT were assessed retrospectively. We used several criteria to define a positive LHBT result. Nine patients received probiotics containing Lactobacillus casei.

Results: Fifty patients were PPI users, 14 were histamine-2 receptor antagonist (H2RA) users, and were 30 non-PPI and non-H2RA users (controls). There were no significant differences in prevalence of LHBT-positive cases among the three groups. Multiple-adjusted regression showed no significant association between PPI use and being LHBT-positive. Prevalence of postprandial fullness in PPI users was high (46%), but such symptoms were not related to LHBT results. Four (44%) of 9 cases became LHBT-negative and the maximal peak of H2 production decreased significantly after probiotic treatment.

Conclusions: PPI treatment is not associated with SIBO in Japanese patients. Mechanisms apart from SIBO could cause the high prevalence of postprandial fullness in PPI users.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Bacteria / metabolism
  • Biomarkers / metabolism
  • Breath Tests*
  • Female
  • Gases
  • Gastroesophageal Reflux / diagnosis
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / epidemiology
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Hydrogen / metabolism*
  • Intestine, Small / drug effects*
  • Intestine, Small / microbiology
  • Japan / epidemiology
  • Lactulose / metabolism*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prevalence
  • Probiotics / therapeutic use
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Time Factors


  • Biomarkers
  • Gases
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors
  • Lactulose
  • Hydrogen