Lactobacillus reuteri Strain Combination In Helicobacter pylori Infection A Randomized, Double-Blind, Placebo-Controlled Study Ruggiero Francavilla, MD, PhD,* Lorenzo Polimeno, PhD,w Antonella Demichina, MD,w Giovanni Maurogiovanni, MD,w Beatrice Principi, MD,w Giuseppe Scaccianoce, MD,z Enzo Ierardi, MD,y Francesco Russo, MD,8 Giuseppe Riezzo, MD,8 Alfredo Di Leo, MD,w Luciano Cavallo, MD,z Antonio Francavilla, MD,8 and James Versalovic, MD, PhD# Goals: The goals of this study were to investigate the role of a new probiotic preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in Helicobacter pylori infection. Background: Specific probiotic strains play a role in H. pylori infection for their ability to decrease bacterial load and gastritis, prevent antibiotic-associated side effects, and increase the erad- ication rate. Study: This is a prospective, double-blind, randomized, placebo- controlled study in a tertiary care setting. A total of 100 H. pylori– positive naive patients received either L. reuteri combination (2  10 8 Colony Forming Units) or placebo during a 3-phase study (pre-eradication, eradication, and follow-up). All underwent 13 C urea breath test ( 13 C-UBT), blood assessments of gastrin-17 (G17), endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was confirmed by 13 C-UBT 8 weeks after the com- pletion of therapy. Results: Fifty patients were allocated in each group. During pre- eradication period, 13 C-UBT d decreased by 13% in L. reuteri combination as compared with a 4% increase in placebo ( 13.2 ± 34% vs. 4.3 ± 27%; P < 0.03). During eradication, GSRS increased significantly in placebo as compared with L. reu- teri combination (6.8 ± 2.9 vs. 4 ± 3.1; P < 0.01). Significantly less patients in L. reuteri combination as compared with placebo- reported side effects (40.9% vs. 62.8%; P < 0.04). An abnormal G17 value was found in patients receiving placebo as compared with L. reuteri combination (28% vs. 12%; P < 0.02). Eradication rate was 75% in L. reuteri combination and 65.9% in placebo (P = NS). L. reuteri combination increased eradication rate by 9.1% (odds ratio: 1.5). Conclusions: L. reuteri combination alone is able to exert an inhibitory effect on H. pylori growth, and when administered with eradication therapy, it determines a significant reduction in anti- biotic-associated side effects. Moreover, L. reuteri combination was able to decrease serum G17 levels and to (not significantly) increase the H. pylori–eradication rate. Key Words: Helicobacter pylori, probiotics, bacterial load, anti- biotic-associated side effects, eradication therapy (J Clin Gastroenterol 2014;48:407–413) H elicobacter pylori is a cause of chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and lymphoma. Eradication prevents peptic ulcer disease recurrence, cures localized low-grade gastric lymphomas, and may revert gastric atrophy. 1 In recent years, we have worldwide wit- nessed the decline in eradication rates to <80%, 2 mainly due to the increase in antibiotic resistance, low compliance to treatment, and antibiotic-associated side effects experi- enced in 5% to 30% of patients. 3 Therefore, there is an increasing need of new regimens to achieve a desirable eradication rate; the Maastricht IV Consensus Report stated that certain probiotics show promising results as adjuvant treatment. 4 Specific probiotics are able to lower H. pylori bacterial load and gastric inflammation and to reduce antibiotic-associated side effects 5 ; however, the effect is restricted to particular strains. No study has assessed all these aspects in a single trial. We have previously reported that Lactobacillus reuteri ATCC 55730 at a daily dose of 10 8 Colony Forming Units (CFU) is able to decrease H. pylori bacterial load 6 and to reduce side effects during anti-H. pylori treatment. 7 This L. reuteri strain was cured of 2 plasmids coding for an unwanted antibiotic resistance, resulting in its daughter strain, L. reuteri DSM 17938. 8 Recently, a new human L. reuteri strain (ATCC PTA 6475) has been characterized; in equipotent concentration to L. reuteri DSM 17938, this strain has strong tolerance to acid 9 and has anti-inflammatory properties not displayed by L. reuteri DSM 17938. 10,11 The rationale to include L. reuteri ATCC PTA 6475 was to investigate whether the addition of an anti-inflammatory strain could have an additional effect in H pylori–infected patients. The aim of the current study was to study the com- bination of a mixture of L. reuteri, DSM 17938 and ATCC Received for publication March 13, 2013; accepted September 16, 2013. From the *Interdisciplinary Department of Medicine, Clinica Pediatrica “B. Trambusti”; wGastroenterology Unit, Department of Emergency and Organ Transplantation; zBiomedical Sciences and Human Oncology (DIMO), University of Bari; zStruttura Semplice Dipar- timentale Endoscopia Digestiva Ospedale “Umberto I” Altamura; 8IRCCS “Saverio De Bellis Castellana Grotte, Bari; yGastroenter- ology Unit, Department Medical & Occupational Sciences, Uni- versity of Foggia, Foggia, Italy; and #Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX. The authors received an unrestricted donation and study products from BioGaia. The study was designed by the authors who were also responsible for collecting data, statistical analyses, interpretation of the data, and writing of the manuscript. Some data have been presented orally at the “UEGW 2013.” The authors declare that they have nothing to disclose. Reprints: Ruggiero Francavilla, MD, PhD, Interdisciplinary Department of Medicine, Clinica Pediatrica “B. Trambusti,” University of Bari, Viale Einaudi, 11 Bari, Italy (e-mail: rfrancavilla@icloud.com). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Website, www.jcge.com. Copyright r 2013 by Lippincott Williams & Wilkins ORIGINAL ARTICLE J Clin Gastroenterol  Volume 48, Number 5, May/June 2014 www.jcge.com | 407