Effects of long-term PPI treatment on producing bowel symptoms and SIBO

Eur J Clin Invest. 2011 Apr;41(4):380-6. doi: 10.1111/j.1365-2362.2010.02419.x. Epub 2010 Dec 3.


Background: Gastroesophageal reflux disease (GERD), including erosive reflux disease and non-erosive reflux disease (NERD), is a chronic disease with a significant negative effect on quality of life. State-of-the-art treatment involves proton pump inhibitors (PPIs). However, relapse of symptoms occurs in the majority of the patients who require recurrent or continuous therapy. Although PPIs are well tolerated, little information is available about gastrointestinal side effects.

Aim: To evaluate the effects of long-term PPI treatment on development of bowel symptoms and/or small intestinal bacterial overgrowth (SIBO).

Methods: Patients with NERD not complaining of bowel symptoms were selected by upper endoscopy, 24-h pH-metry and a structured questionnaire concerning severity and frequency of bloating, flatulence, abdominal pain, diarrhoea and constipation. Patients were treated with esomeprazole 20 mg bid for 6 months. Prior to and after 8 weeks and 6 months of therapy, patients received the structured questionnaire and underwent evaluation of SIBO by glucose hydrogen breath test (GHBT).

Results: Forty-two patients with NERD were selected out of 554 eligible patients. After 8 weeks of PPI treatment, patients complained of bloating, flatulence, abdominal pain and diarrhoea in 43%, 17%, 7% and 2%, respectively. After 6 months, the incidence of bowel symptoms further increased and GHBT was found positive in 11/42 (26%) patients. By a post hoc analysis, a significant (P < 0·05) percentage of patients (8/42) met Rome III criteria for irritable bowel syndrome.

Conclusions: Prolonged PPI treatment may produce bowel symptoms and SIBO; therefore, the strategy of step-down or on-demand PPI therapy should be encouraged in GERD.

MeSH terms

  • Adult
  • Esomeprazole / adverse effects*
  • Female
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / physiopathology
  • Humans
  • Intestines / drug effects*
  • Intestines / microbiology
  • Irritable Bowel Syndrome / chemically induced*
  • Irritable Bowel Syndrome / physiopathology
  • Italy
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / adverse effects*
  • Time Factors


  • Proton Pump Inhibitors
  • Esomeprazole