Systematic Reviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Apr 26, 2015; 3(2): 97-117
Published online Apr 26, 2015. doi: 10.13105/wjma.v3.i2.97
Meta-analysis of single strain probiotics for the eradication of Helicobacter pylori and prevention of adverse events
Lynne V McFarland, Peter Malfertheiner, Ying Huang, Lin Wang
Lynne V McFarland, Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, United States
Lynne V McFarland, Health Services Research and Development, VA Puget Sound Health Care System, Department of Veterans Affairs, Seattle, WA 98101, United States
Peter Malfertheiner, Universitatsklinikum Magdeburg AOR, 39120 Magdeburg, Germany
Ying Huang, Lin Wang, Children’s Hospital of Fudan University, Shanghai 201102, China
Author contributions: McFarland LV, Malfertheiner P, Huang Y and Wang L reviewed, scored papers and were involved in the manuscript preparation; McFarland LV designed the study, did literature search and analyzed the data.
Conflict-of-interest: Lynne V McFarland has received fees as a speaker (Biocodex, France and Lallemand, France) and is on the scientific advisory board of BioK+, Canada. Peter Malfertheiner has received speaker fees from Biocodex and is on the scientific advisor board of Danone. Ying Huang and Lin Wang have no conflicts of interest. No authors are employed by or have stock or equity in any company manufacturing probiotics.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lynne V McFarland, PhD, Health Services Research and Development, VA Puget Sound Health Care System, Department of Veterans Affairs, Metropolitan Park West, 1100 Olive Way #1400, Seattle, WA 98101, United States. lvmcfarl@u.washington.edu
Telephone: +1-206-2771780 Fax: +1-206-7642935
Received: October 22, 2014
Peer-review started: October 24, 2014
First decision: December 26, 2014
Revised: January 3, 2015
Accepted: January 15, 2015
Article in press: January 19, 2015
Published online: April 26, 2015
Processing time: 187 Days and 10.3 Hours
Abstract

AIM: To assess the efficacy and safety of single strain probiotics for the: (1) eradication of Helicobacter pylori (H. pylori); (2) prevention of adverse events; and (3) prevention of antibiotic-associated diarrhea associated with eradication therapy.

METHODS: We searched PubMed (1960-2014), EMBASE (1974-2014), Cochrane Database of Systematic Reviews (1990-2014), and ISI Web of Science (2000-2014). Additionally, we conducted a grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroenterology meetings, experts in the field and correspondence with authors. Randomized controlled trials of H. pylori positive adults or children treated with eradication therapy and assessing the adjunctive therapy with a single strain of probiotics were included. The primary outcomes were the rates of eradication of H. pylori and frequency of patients with adverse events or antibiotic-associated diarrhea. Outcomes were pooled using fixed or random-effects models to calculate the relative risk and corresponding 95%CI and weighted on study size. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on daily probiotic dose, study population, and quality of the study. The overall quality of the evidence for each probiotic strain was assessed using the GRADE criteria.

RESULTS: A total of 25 randomized controlled trials (28 treatment arms, with a total of 3769 participants) assessed one of six single probiotic strains as adjunctive treatments to standard eradication therapy. Only one probiotic strain significantly improved H. pylori eradication rates: Saccharomyces boulardii (S. boulardii) CNCM I-745 [pooled relative risks (pRR) = 1.11, 95%CI: 1.07-1.16]. Only one probiotic strain (S. boulardii CNCM I-745) significantly prevented any adverse events (pRR = 0.42, 95%CI: 0.28-0.62). Both S. boulardii CNCM I-745 and Lactobacillus rhamnosus GG significantly reduced antibiotic-associated diarrhea (pRR = 0.47, 95%CI: 0.37-0.60 and pRR = 0.29, 95%CI: 0.17-0.48, respectively) associated with H. pylori eradication therapy. Meta-regression of sub-groups did not detect significant differences by dose, adult vs pediatric, symptom status, or study quality, but did find significant differences by the strain of probiotic. Potential mild publication bias was found for antibiotic-associated diarrhea, but not for eradication or adverse event outcomes. Analysis of the study quality illuminated areas for improvement in future studies (use of placebos, study size calculations, attrition reasons and discussion of limitations and generalizability).

CONCLUSION: The pooled evidence suggests that the adjunctive use of a few probiotic strains may improve H. pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea in those treated with standard eradication therapies. The type of probiotic strain was the most important factor in predicting efficacy.

Keywords: Probiotics; Safety; Saccharomyces boulardii; Helicobacter pylori; Meta-analysis; Adverse reactions; Diarrhea; Lactobacillus rhamnosus; Randomized clinical trials

Core tip: A meta-analysis was conducted (1960-2014) for randomized clinical trials testing single strained probiotics as an adjunct to standard Helicobacter pylori (H. pylori) eradication therapy. Of the single strains with multiple trials, only one significantly improved H. pylori eradication rates {Saccharomyces boulardii (S. boulardii) I-745 [pooled relative risks (pRR) = 1.11, 95%CI: 1.07-1.16)]}, while two strains significantly reduced the rate of antibiotic-associated diarrhea [S. boulardii I-745 (pRR = 0.47, 95%CI: 0.37-0.60) and Lactobacillus rhamnosus GG (pRR = 0.29, 95%CI: 0.17-0.48)]. None of the other four probiotic strains improved H. pylori therapy (C. butyricum, L. acidophilus, L. reuteri, L. casei).