Efficacy Of Probiotic Of Supplementation Therapy In Helicobacter Pylori Eradication: A Meta-analysis Of Randomized-controlled Trials

Objective: To systematic evaluate the effect of probiotics supplementation on improving eradication rates and minimizing therapy-associated adverse events in anti-Helicobacter pylori regimens.Methods : We sought eligible randomized controlled trials in Pub Med,Medline,Cochrane Central Trials,Chinese Biological Medicine database and Chinese National Knowledge Infrastructure electronic databases published from there inception until July,2015.All statistical analysis using Review Manager 5.3 software completed.Results: Thirteen randomized controlled trials involving a total of 2306 patients were included in our analysis.(1)The pooled relative risk(RR)of eradication rates by intent to treat analysis in probiotics treatment groups was obviously higher than controls groups [RR 1.15,95% confidence interval(CI): 1.10-1.20,P<0.00001],using fixed effects model without significant publication bias(test for heterogeneity I2=45%).(2)The incidence of total antibiotics-related side effects also reduced in the probiotics treatment groups versus control groups,and the pooled RR(studies n=9)was 0.71(95%CI: 0.54-0.94,P=0.02)by 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 rate in probiotics supplementation groups.(3)In subgroup analysis:(1)we found that eradication rates in the probiotics groups 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)without regional differences in Europe(RR=1.17,95% CI: 1.09-1.24,P<0.00001)or Asia(RR=1.14,95% CI: 1.06-1.22,P=0.0002).However,total adverse events were not decreased in the adults groups(RR=0.80,95% CI:0.61-1.04,P=0.1)and Asian groups(RR=0.68,95% CI: 0.39-1.18,P=0.17).(2)In subgroup analysis that examined therapy regiments and duration of treatment,probiotics application to the treatment increased the eradication rates in triple therapy(RR=1.18,95% CI: 1.12-1.25,P<0.00001),seven-days-treatment(RR=1.21,95% CI: 1.12-1.31,P<0.00001)and fourteen-days-treatment(RR=1.13,95% CI: 1.06-1.20,P=0.0002).The antibiotic-associated side effects were significantly reduced with the exception of the quadruple therapy subgroup(RR=1.13,95% CI: 0.60-2.13,P=0.07)and fourteen-days-therapy subgroup(RR=0.96,95% CI 0.61-1.51,P=0.86).(3)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)were effective in improving H.pylori eradication rates.However,supplementation with lactobacillus alone did not obviously decrease overall side effects(RR=0.61,95% CI: 0.11-3.51,P=0.58).(4)The study also showed that probiotics supplementation simultaneously with,prior to or subsequent to the H.pylori eradication therapy improved eradication rates,regardless of the duration.Furthermore,only supplementing probiotics simultaneously with the H.pylori treatment could reduce side effects.Conclusion:(1)Supplementation with probiotics in anti-Helicobacter pylori regimens could be effective in improving H.pylori eradication rates,minimizing total therapy-associated adverse events and alleviating most clinical symptoms.(2)Supplementation with probiotics in anti-Helicobacter pylori regimens have no restricitions of age and region,significantly improvement in the eradication rate all performenced in the adults and children from Europe or Asia,but the total adverse events were significantly decreased only in the Europe and children.(3)Supplementation with probiotics in the triple regimen could increased eradication rates and reduced most antibiotics-related side effects,so,for patients who can not tolerate fourteen-days treatment,seven-days standard triple therapy and supplementation with probiotics maybe the better choice in eradication of H.pylori.(4)Supplementation with multi-strain probiotics as adjuncts have more beneficial to H.pylori eradication result from the significantly reduced antibiotics-related adverse events.(5)In anti-H.pylori regimens simultaneously supplement with one week probiotics maybe a relatively better treatment.