11, 12 and 13 Efficacy has also been reported for some strains, such as Lactobacillus shirota, in SBBO. 14 Probiotics’ mechanisms of action consist of competition with harmful bacteria, synthesis of antimicrobial conjugate (bacteriocin, lactic acid, organic acid, microsin, reuterin, and volatile fatty acid), stimulation of the immune response, and stimulation of the intestinal epithelium through production of short chain fatty acids. 15, 16, 17, 18 and 19 Until now, studies on the role of probiotics in prevention and therapy of SBBO in children are very limited. The aims of this study were to test whether PPIs induce SBBO in children, and to evaluate

whether the probiotic strains tested can prevent the development of SBBO. This double-blinded, placebo-controlled TGF-beta inhibitor randomized GSK1349572 order clinical trial was conducted in children ≥ 5 years old seen mainly because of complaints of epigastric pain in the Outpatient Clinic of the Cipto Mangunkusumo Hospital. When it was decided, on clinical grounds, that the presenting symptoms justified a therapeutic trial with omeprazole, and in the absence

of exclusion criteria, a glucose breath test was performed to rule out SBBO prior to PPI-therapy. All the subjects were treated with 20 mg of oral omeprazole daily for four weeks. Patients swallowed the intact omeprazole capsule; patients with difficulties to swallow the capsule were allowed to open it and swallow the microgranules in media such as orange juice or berry juice. Furthermore, the patients were randomized in two groups: group A (probiotic group) received one probiotic capsule per day during four weeks, while group B (control group) was given a placebo capsule. The probiotic used is Lacidofil®, which contains 1.9 × 109 cfu Lactobacillus rhamnosus R0011 and 0.1 × 109 cfu Lactobacillus

acidophillus R0052. A cold chain for the administration of the probiotic was preserved, as the probiotics were stored in a cooler and transported using a cold chain bag with gel ice packs inside. The following patients were excluded: known SBBO; treatment with anti-acid agents or antibiotics during the past two weeks; immune suppression (steroid treatment, antituberculosis therapy, antiretroviral, or Thalidomide cytostatics); or warfarin, phenytoin or diazepam use. Observation for medication compliance (PPI and probiotic/placebo) was performed twice a week through phone, by asking the parents about compliance. Subjects who did not take their medication during at least three days during the four-week intervention period were considered as “poor compliant”. A second glucose breath test was performed four to ten days after the end of therapy. The patients fasted for ten to 12 hours, and brushed their teeth in the morning prior to the examination. The breath test started by measuring the baseline hydrogen; the latter had to be < 10 ppm to be considered as normal (Gastrolyzer2, Bedfont Scientific Ltd.