Skip to main content
Springer Nature Link
Log in

Efficacy and safety of probiotic-supplemented triple therapy for eradication of Helicobacter pylori in children: a systematic review and network meta-analysis

  • Review
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aim

The aim of this study was to identify the best probiotic supplementation in triple therapy for pediatric population with Helicobacter pylori infection.

Methods

Eligible trials were identified by comprehensive searches. Relative risks with 95% confidence intervals and relative ranks with P scores were assessed.

Results

Twenty-nine trials (3122 participants) involving 17 probiotic regimens were identified. Compared with placebo, probiotic-supplemented triple therapy significantly increased H. pylori eradication rates (relative ratio (RR) 1.19, 95% CI 1.13–1.25) and reduced the incidence of total side effects (RR 0.49, 95% CI 0.38–0.65). Furthermore, to supplemented triple therapy, Lactobacillus casei was identified the best for H. pylori eradication rates (P score = 0.84), and multi-strain of Lactobacillus acidophilus and Lactobacillus rhamnosus for total side effects (P score = 0.93). As for the subtypes of side effects, multi-strain of Bifidobacterium infantis, Bifidobacterium longum, L. acidophilus, L. casei, Lactobacillus plantarum, Lactobacillus reuteri, L. rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, and Streptococcus thermophilus was the best to reduce the incidence of diarrhea; multi-strain of Bacillus mesentericus, Clostridium butyricum, and Streptococcus faecalis for loss of appetite; multi-strain of B. longum, Lactobacillus bulgaricus, and S. thermophilus for constipation; multi-strain of Bifidobacterium bifidum, B. infantis, L. acidophilus, L. bulgaricus, L. casei, L. reuteri, and Streptococcus for taste disturbance; Saccharomyces boulardii for bloating; and multi-strain of Bifidobacterium breve, B. infantis, L. acidophilus, L. bulgaricus, L. casei, L. rhamnosus, and S. thermophilus for nausea/vomiting.

Conclusions

Probiotics are recommended to supplement triple therapy in pediatrics, and the effectiveness of triple therapy is associated with specific probiotic supplementation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Go MF (2002) Review article: natural history and epidemiology of Helicobacter pylori infection. Aliment Pharmacol Ther 1:3–15

    Article  Google Scholar 

  2. Frenck RW Jr, Clemens J (2003) Helicobacter in the developing world. Microbes Infect 5(8):705–713

    Article  PubMed  Google Scholar 

  3. Goldman CG, Barrado DA, Balcarce N, Rua EC, Oshiro M, Calcagno ML, Janjetic M et al (2006) Effect of a probiotic food as an adjuvant to triple therapy for eradication of Helicobacter pylori infection in children. Nutrition 22(10):984–988

    Article  PubMed  Google Scholar 

  4. Olmos JA, Rios H, Higa R (2000) Prevalence of Helicobacter pylori infection in Argentina: results of a nationwide epidemiologic study. Argentinian Hp Epidemiologic Study Group. J Clin Gastroenterol 31(1):33–37

    Article  CAS  PubMed  Google Scholar 

  5. Akcam M, Koca T, Salman H, Karahan N (2015) The effects of probiotics on treatment of Helicobacter pylori eradication in children. Saudi Med J 36(3):286–290

    Article  PubMed  PubMed Central  Google Scholar 

  6. Koletzko S, Jones NL, Goodman KJ, Gold B, Rowland M, Cadranel S, Chong S et al (2011) Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr 53(2):230–243

    PubMed  Google Scholar 

  7. Oderda G, Shcherbakov P, Bontems P, Urruzuno P, Romano C, Gottrand F, Gomez MJ et al (2007) Results from the pediatric European register for treatment of Helicobacter pylori (PERTH). Helicobacter 12(2):150–156

    Article  PubMed  Google Scholar 

  8. Kawakami E, Ogata SK, Portorreal AC, Magni AM, Pardo ML, Patricio FR (2001) Triple therapy with clarithromycin, amoxicillin and omeprazole for Helicobacter pylori eradication in children and adolescents. Arq Gastroenterol 38(3):203–206

    Article  CAS  PubMed  Google Scholar 

  9. Lu MH, Yu S, Deng JQ, Yan Q, Yang C, Xia GD, Zhou X (2016) Efficacy of probiotic supplementation therapy for Helicobacter pylori eradication: a meta-analysis of randomized controlled trials. PLoS One 11(10):26

    Google Scholar 

  10. Li S, Huang XL, Sui JZ, Chen SY, Xie YT, Deng Y, Wang J et al (2014) Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children. Eur J Pediatr 173(2):153–161

    Article  PubMed  Google Scholar 

  11. Zheng X, Lyu L, Mei ZC (2013) Lactobacillus-containing probiotic supplementation increases Helicobacter pylori eradication rate: evidence from a meta-analysis. Rev Esp Enferm Dig 105(8):445–453

    Article  PubMed  Google Scholar 

  12. Szajewska H, Horvath A, Piwowarczyk A (2010) Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment. Aliment Pharmacol Ther 32(9):1069–1079

    Article  CAS  PubMed  Google Scholar 

  13. McFarland LV, Huang Y, Wang L, Malfertheiner P (2016) Systematic review and meta-analysis: multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events. United European Gastroenterol J 4(4):546–561

    Article  CAS  PubMed  Google Scholar 

  14. McFarland LV, Malfertheiner P, Huang Y, Wang L (2015) Meta-analysis of single strain probiotics for the eradication of Helicobacter pylori and prevention of adverse events. World J Metaanal 3(2):97–117

    Google Scholar 

  15. Szajewska H (2016) What are the indications for using probiotics in children? Arch Dis Child 101(4):398–403

    Article  PubMed  Google Scholar 

  16. Drumm B, Koletzko S, Oderda G (2000) Helicobacter pylori infection in children: a consensus statement. European Paediatric Task Force on Helicobacter pylori. J Pediatr Gastroenterol Nutr 30(2):207–213

    Article  CAS  PubMed  Google Scholar 

  17. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12

    Article  CAS  PubMed  Google Scholar 

  18. Rucker G (2012) Network meta-analysis, electrical networks and graph theory. Res Synth Methods 3(4):312–324

    Article  PubMed  Google Scholar 

  19. Schwarzer G, Carpenter JR, Rucker G (2015) Meta-analysis with R (Use-R!). Springer International Publishing, Switzerland

    Book  Google Scholar 

  20. Rucker G, Schwarzer G (2015) Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med Res Methodol 15–58

  21. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  PubMed  Google Scholar 

  22. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, Ioannidis JP et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162(11):777–784

    Article  PubMed  Google Scholar 

  24. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6(7):e1000100

    Article  PubMed  PubMed Central  Google Scholar 

  25. Li Z (2009) Efficacy of sequential triple therapy combined with probiotics in the treatment of Helicobacter pylori infection in children. Chin Prev Med 10(8):728–729

    Google Scholar 

  26. Pan TT, ZHU H, Lu H (2010) Clinical observation on the effect of probiotics in the treatment of Helicobacter pylori infection in children. Strait Pharma J 22(2):109–110

    Google Scholar 

  27. Wang WJ, Luo H, Wei J (2011) Effect of probiotics on Helicobacter pylori eradication in children with abdominal pain. Chin J Microecol 23(10):916–917

    Google Scholar 

  28. Zhang Y, Li J (2012) Effect of Saccharomyces boulardii on treatment of Helicobacter pylori infection in children of triple therapy. J Clin Pediatr 30(10):928–931

    CAS  Google Scholar 

  29. Zhou YJ (2012) Clinical observation of the effect of Helicobacter pylori eradication in children with Helicobacter pylori infection. Chin J Integr Trad West Med Dig 20(10):458–459

    Google Scholar 

  30. Yang Y, Huang J, Shao S (2013) Efficacy of probiotics combined with triple therapy in treatment of Helicobacter pylori infection in children. Chin J Nosocomiol 23(23):5757–5758

    Google Scholar 

  31. Zhang H (2013) Clinical effect about Boulardii powder combined triple therapy treating Helicobacter pylori infection in children. Medical J Chin People Health 25(1):38–40

    Google Scholar 

  32. He AZ (2014) Efficacy of probiotics combined with triple therapy in treatment of Helicobacter pylori infection in children. World Health Dig 14(19):122

    Google Scholar 

  33. Li M, Zhou X (2014) Efficacy of triple therapy combined with probiotics in the treatment of Helicobacter pylori infection in children. Modern J Integr Trad Chin West Med 23(26):2883–2884

    Google Scholar 

  34. Wang HJ, Feng D (2014) The effect of multi-drug combination in treatment of children with active gastric ulcer. Chin Med Herald 11(26):58–61

    Google Scholar 

  35. Yang XL (2014) The clinical trial on the eradication of Helicobacter pylori using probiotics with standard triple therapy on children. China Medical University, Dissertation

    Google Scholar 

  36. Peng HM, Mei H, Wang B (2015) Efficacy of quadruple therapy containing probiotics on Helicobacter pylori. J Chin Physician 17(8):1249–1251

    Google Scholar 

  37. Sun BB (2015) Clinical effect of probiotics combined with triple therapy on Helicobacter pylori infection in children. Chin Med Herald 12(20):125–122

    Google Scholar 

  38. Zhong HZ, Ye Y, Lv B (2015) Clinical observation of the application of probiotics combined with triple therapy in the treatment of Helicobacter pylori infection in children. Chin Med Engineering 23(11):144–146

    Google Scholar 

  39. Fan J, Li M, Liao J (2016) Probiotics combined with triple therapy in the treatment of Helicobacter pylori infection in children. J Modern Clin Med 42(2):114–116

    Google Scholar 

  40. Xu LF, Yang X, Guo J (2016) Randomized controlled trial of Clostridium butyricum in eradication treatment of Helicobacter pylori infection in children. Chin J Microecol 28(4):413–416

    Google Scholar 

  41. Pan XL (2015) Effect of probiotics combined with triple therapy clinical value in treatment of Helicobacter pylori associated chronic gastritis. J Qiqihar University Med 36(24):3627–3629

    Google Scholar 

  42. Saneeyan H, Layegh S, Rahimi H (2011) Effectivness of probiotic on treatment of Helicobacter pylori infection in children. J Isfahan Med Sch 29(146):882–889

    Google Scholar 

  43. Sykora J, Valeckova K, Amlerova J, Siala K, Dedek P, Watkins S, Varvarovska J et al (2005) Effects of a specially designed fermented milk product containing probiotic Lactobacillus casei DN-114 001 and the eradication of H. pylori in children: a prospective randomized double-blind study. J Clin Gastroenterol 39(8):692–698

    Article  CAS  PubMed  Google Scholar 

  44. Szajewska H, Albrecht P, Topczewska-Cabanek A (2009) Randomized, double-blind, placebo-controlled trial: effect of Lactobacillus GG supplementation on Helicobacter pylori eradication rates and side effects during treatment in children. J Pediatr Gastroenterol Nutr 48(4):431–436

    Article  CAS  PubMed  Google Scholar 

  45. Ahmad K, Fatemeh F, Mehri N, Maryam S (2013) Probiotics for the treatment of pediatric Helicobacter pylori infection: a randomized double blind clinical trial. Iran J Pediatr 23(1):79–84

    PubMed  Google Scholar 

  46. Bin Z, Ya-Zheng X, Zhao-Hui D, Bo C, Li-Rong J, Vandenplas Y (2015) The efficacy of Saccharomyces boulardii CNCM I-745 in addition to standard Helicobacter pylori eradication treatment in children. Pediatr Gastroenterol Hepatol Nutr 18(1):17–22

    Article  PubMed  PubMed Central  Google Scholar 

  47. Hurduc V, Plesca D, Dragomir D, Sajin M, Vandenplas Y (2009) A randomized, open trial evaluating the effect of Saccharomyces boulardii on the eradication rate of Helicobacter pylori infection in children. Acta Paediatr 98(1):127–131

    Article  CAS  PubMed  Google Scholar 

  48. Tolone S, Pellino V, Vitaliti G, Lanzafame A, Tolone C (2012) Evaluation of Helicobacter pylori eradication in pediatric patients by triple therapy plus lactoferrin and probiotics compared to triple therapy alone. Ital J Pediatr 38(63)

  49. Zhao HM, Ou-Yang HJ, Duan BP, Xu B, Chen ZY, Tang J, You JY (2014) Clinical effect of triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori infection in children. Zhongguo Dang Dai Er Ke Za Zhi 16(3):230–233

    PubMed  Google Scholar 

  50. Wang YH, Huang Y (2014) Effect of Lactobacillus acidophilus and Bifidobacterium bifidum supplementation to standard triple therapy on Helicobacter pylori eradication and dynamic changes in intestinal flora. World J Microbiol Biotechnol 30(3):847–853

    Article  CAS  PubMed  Google Scholar 

  51. Plewińska EM, Płaneta-Małecka I, Bąk-Romaniszyn L, Małecka-Panas E (2006) Probiotics in the treatment of Helicobacter pylori infection in children. Gastroenterol Polska 13(4):315–319

  52. Mack DR, Michail S, Wei S, McDougall L, Hollingsworth MA (1999) Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol 276(4 Pt 1):G941–G950

    CAS  PubMed  Google Scholar 

  53. Haller D, Bode C, Hammes WP, Pfeifer AM, Schiffrin EJ, Blum S (2000) Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures. Gut 47(1):79–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Del Piano M, Anderloni A, Balzarini M, Ballare M, Carmagnola S, Montino F, Orsello M et al (2012) The innovative potential of Lactobacillus rhamnosus LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01, and Lactobacillus delbrueckii subsp delbrueckii LDD01 to restore the “gastric barrier effect” in patients chronically treated with PPI: a pilot study. J Clin Gastroenterol 46(9):S18–S26

    Article  PubMed  Google Scholar 

  55. Wang KY, Li SN, Liu CS, Perng DS, Su YC, Wu DC, Jan CM et al (2004) Effects of ingesting Lactobacillus- and Bifidobacterium-containing yogurt in subjects-with colonized Helicobacter pylori. Am J Clin Nutr 80(3):737–741

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Jue-Rong Feng and Fan Wang contributed equally to the study.

Authors and Affiliations

  1. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, China

    Jue-Rong Feng, Fan Wang, Xiao Qiu, Peng-Fei Chen, Rui Zhou, Jing Liu, Qiu Zhao & Jin Li

  2. Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, No. 169, Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, China

    Jue-Rong Feng, Fan Wang, Xiao Qiu, Peng-Fei Chen, Rui Zhou, Jing Liu, Qiu Zhao & Jin Li

  3. Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA, 98115, USA

    Lynne V. McFarland

  4. Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China

    Peng-Fei Chen

Authors
  1. Jue-Rong Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lynne V. McFarland
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peng-Fei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qiu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Jue-Rong Feng and Dr. Fan Wang conceived and designed the search strategy, ran the searches, selected the studies, extracted the raw data, analyzed the data, and drafted and revised the manuscript.

Dr. Peng-Fei Chen and Dr. Rui Zhou independently assessed the risk of bias and checked the extracted data.

Professor Jing Liu and Dr. Xiao Qiu designed the data collection instruments; supervised the searches, data collection, and analysis; and critically reviewed the manuscript. Dr. Lynne V. McFarland provided the additional data and assisted with the manuscript writing.

Professor Qiu Zhao and Professor Jin Li conceptualized and designed the study, supervised the searches and data analysis, and revised the manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Qiu Zhao or Jin Li.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

ESM 1

(DOCX 28 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, JR., Wang, F., Qiu, X. et al. Efficacy and safety of probiotic-supplemented triple therapy for eradication of Helicobacter pylori in children: a systematic review and network meta-analysis. Eur J Clin Pharmacol 73, 1199–1208 (2017). https://doi.org/10.1007/s00228-017-2291-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-017-2291-6

Keywords

Search

Navigation