Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care

Minerva Gastroenterol (Torino). 2023 Dec;69(4):523-528. doi: 10.23736/S2724-5985.21.03118-1. Epub 2023 Mar 21.


Background: Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH<inf>4</inf>) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients.

Methods: One hundred twenty-five gastroesophageal reflux disease patients, constantly treated with PPI for at least 6 months and undergoing to LBT, were retrospectively assessed. An age-matched control population (control) of 100 patients, which had not used PPI in the last 6 months, was also enrolled. In the PPI group, SIBO positive patients and CH<inf>4</inf> producers were treated with rifaximin 1200 mg/daily for 14 days and re-checked with LBT one month after the end of treatment. The area under the curve (AUC) before and after treatment was also calculated for both SIBO positive patients and CH<inf>4</inf> producers.

Results: In the PPI group, SIBO prevalence was significantly higher vs. controls (38/125 [30.4%] vs. 27/100 [27%], P<0.05). 77/125 (61.6%) PPI patients were found to be CH<inf>4</inf> producers vs. 21/100 (21%) controls (P<0.05). Among SIBO patients in the PPI group, 34 (89.4%) were also CH<inf>4</inf> producers vs. 17/27 (63%) controls (P<0.05). After treatment, LBT resulted negative in 15/22 SIBO patients (68.1%) (P<0.05) and in 18/34 CH<inf>4</inf> producers (52.9%) (P<0.05). At the AUC analysis, an overall reduction of 54.2% for H<inf>2</inf> in SIBO patients and of 47.7% for CH<inf>4</inf> was assessed after rifaximin treatment (P<0.05).

Conclusions: Our data showed that chronic use of PPI could be able to increase the prevalence of SIBO and to shift the intestinal microbial composition towards a CH4-producing flora. rifaximin could represent a useful therapeutical option for PPI-induced SIBO and for modulating CH4-producing flora.

MeSH terms

  • Child
  • Humans
  • Intestine, Small*
  • Lactulose / therapeutic use
  • Methane
  • Prevalence
  • Primary Health Care
  • Proton Pump Inhibitors* / adverse effects
  • Retrospective Studies
  • Rifaximin / therapeutic use


  • Rifaximin
  • Proton Pump Inhibitors
  • Lactulose
  • Methane