title: Efficacy of Probiotic Supplementation Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Traditional Helicobacter pylori (H. pylori) eradication therapies have shown efficacies below 80% in several studies, and their use has been accompanied by antibiotic-related side effects. Some recent studies have reported that supplementing standard therapies with probiotics can improve the efficacy and tolerability of Helicobacter pylori eradication therapy.
  
  
  OBJECTIVE
  To assess the effects of probiotic supplementation on the eradication rates and therapy-related adverse event rates of anti-Helicobacter pylori regimens.
  
  
  METHODS
  We searched PubMed, Medline, the Cochrane Central Registry of Controlled Trials and the Chinese Biomedical Database for eligible randomized controlled trials published through July, 2015. Review Manager 5.3 was used for all statistical analyses.
  
  
  RESULTS
  Thirteen randomized controlled trials involving a total of 2306 patients were included in our analysis. Intent-to-treat (ITT) analysis performed using a fixed-effects model (test for heterogeneity I2 = 45%) showed that the pooled relative risk (RR) of eradication was significantly higher in the probiotic supplementation group than in the control group [RR 1.15, 95% confidence interval (CI): 1.10-1.20, P<0.00001]. The incidence of total antibiotic-related side effects was lower in the probiotic supplementation group than in the control group, and the pooled RR (studies n = 9) was 0.71 (95% CI: 0.54-0.94, P = 0.02), as determined using a random-effects model (heterogeneity test I2 = 59%). Certain adverse events, such as nausea and vomiting (RR = 0.58, 95% CI 0.35-0.95, P = 0.03), diarrhea (RR = 0.51, 95% CI: 0.31-0.84, P = 0.008) and constipation (RR = 0.47, 95% CI: 0.28-0.80, P = 0.005), were reported at lower rates in the probiotic supplementation group than in the control group. Subgroup analysis showed that eradication rates were significantly improved in both adults (RR = 1.14, 95% CI: 1.09-1.19, P<0.00001) and children (RR = 1.24, 95% CI: 1.05-1.47, P = 0.01) in the probiotic supplementation group and that no regional differences between Europe (RR = 1.17, 95% CI: 1.09-1.24, P<0.00001) and Asia were present (RR = 1.14, 95% CI: 1.06-1.22, P = 0.0002). However, the total adverse event rate was not decreased in the adult group (RR = 0.80, 95% CI: 0.61-1.04, P = 0.1) or the Asian group (RR = 0.68, 95% CI: 0.39-1.18, P = 0.17). Subgroup analyses examining therapy regimens and treatment durations showed that probiotic supplementation increased eradication rates in the triple-therapy (RR = 1.18, 95% CI: 1.12-1.25, P<0.00001), seven-day treatment (RR = 1.21, 95% CI: 1.12-1.31, P<0.00001) and fourteen-day treatment (RR = 1.13, 95% CI: 1.06-1.20, P = 0.0002) groups. The incidence of antibiotic-related side effects was significantly reduced in all groups, with the exception of the quadruple-therapy subgroup (RR = 1.13, 95% CI: 0.60-2.13, P = 0.07) and the fourteen-day therapy subgroup (RR = 0.96, 95% CI 0.61-1.51, P = 0.86). Supplementation with Lactobacillus alone (RR = 1.24, 95% CI: 1.12-1.38, P<0.0001) or multi-strain probiotics (RR = 1.12, 95% CI 1.07-1.18, P<0.00001) was effective at improving H. pylori eradication rates. However, supplementation with Lactobacillus alone did not significantly decrease the overall incidence of side effects (RR = 0.61, 95% CI: 0.11-3.51, P = 0.58). Our study also showed that probiotic supplementation before, during or after H. pylori eradication therapy improved eradication rates, regardless of supplementation duration. Furthermore, probiotic supplementation during H. pylori treatment reduced the incidence of side effects.
  
  
  CONCLUSIONS
  Probiotic supplementation during anti-Helicobacter pylori treatment may be effective for improving H. pylori eradication rates, minimizing the incidence of therapy-related adverse events and alleviating most disease-related clinical symptoms. However, our results should be interpreted with caution because of the presence of heterogeneity across the trials included in this analysis.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Southwest Medical University, Sichuan, People's Republic of China.
authors.forename: Muhan
authors.initials: M
authors.lastname: Lü
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Southwest Medical University, Sichuan, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Foreign Languages, Southwest Medical University, Sichuan, People's Republic of China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Southwest Medical University, Sichuan, People's Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Southwest Medical University, Sichuan, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Southwest Medical University, Sichuan, People's Republic of China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Southwest Medical University, Sichuan, People's Republic of China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements; D005260:Female; D016481:Helicobacter Infections / Q000628:therapy*; D016480:Helicobacter pylori; D006801:Humans; D007223:Infant; D008297:Male; D019936:Probiotics / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic