Effectiveness of Saccharomyces boulardii and Metronidazole for Small Intestinal Bacterial Overgrowth in Systemic Sclerosis

Dig Dis Sci. 2020 Apr;65(4):1134-1143. doi: 10.1007/s10620-019-05830-0. Epub 2019 Sep 23.


Background: Small intestinal bacterial overgrowth (SIBO) affects up to 60% of patients with systemic sclerosis (SSc), and it improves with antibiotics. The addition of probiotics could lead to better results.

Aims: To evaluate the efficacy and safety of Saccharomyces boulardii (SB) versus metronidazole (M) versus M + SB for 2 months, to reduce gastrointestinal symptoms and SIBO assessed with hydrogen breath test in SSc.

Methods: An open pilot clinical trial performed in forty patients with SIBO and SSc (ACR-EULAR 2013) who signed informed consent. Three groups were assigned: M, SB, and M + SB, for 2 months. Hydrogen was measured in parts per million with a hydrogen breath test to evaluate SIBO. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) questionnaire was applied to quantify gastrointestinal symptoms with a raw score of eight symptoms. This study is registered in ClinicalTrials.gov with the following ID: NCT03692299.

Results: Baseline characteristics were similar between groups. The average age was 53.2 ± 9.3 years, and the evolution of SSc was 13.5 (1-34) years. After 2 months of treatment, SIBO was eradicated in 55% of the M + SB group: 33% of SB, and 25% of M. The SB and M + SB groups had decreased diarrhea, abdominal pain, and gas/bloating/flatulence, but M remained unchanged. Reductions in expired hydrogen at 45 to 60 min were as follows: M + SB 48% and 44%, M 18% and 20%, and SB 53% and 60% at the first and second months, respectively (p < 0.01). Adverse effects were epigastric burning and constipation in M (53%) and M + SB (36%), and flatulence/diarrhea in SB (22%).

Conclusions: Metronidazole treatment is partially effective in SIBO, but S. boulardii in monotherapy or in combination improves the gastrointestinal outcomes in SSc.

Keywords: Bacterial overgrowth syndrome; Hydrogen; Metronidazole; Saccharomyces; Systemic scleroderma; Systemic sclerosis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Bacterial Infections / diagnosis
  • Bacterial Infections / therapy*
  • Female
  • Humans
  • Intestine, Small / drug effects
  • Intestine, Small / microbiology*
  • Male
  • Metronidazole / administration & dosage*
  • Middle Aged
  • Pilot Projects
  • Probiotics / administration & dosage
  • Saccharomyces boulardii*
  • Scleroderma, Systemic / diagnosis
  • Scleroderma, Systemic / microbiology*
  • Scleroderma, Systemic / therapy*
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Metronidazole

Associated data

  • ClinicalTrials.gov/NCT03692299