Skip to main content

Advertisement

SpringerLink
Log in

Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials

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

Abstract

Therapy-related side effects and severe antimicrobial resistance still remain an obstacle to Helicobacter pylori eradication. This meta-analysis aimed to investigate the efficacy of Lactobacillus-supplemented triple therapy on H. pylori eradication rates and therapy-related side effects in children. Five studies involving 484 pediatric patients were included in our analysis. The pooled relative risk (RR) for eradication rates in the Lactobacillus group versus the control group was 1.19 [95% confidence interval (CI) 1.07–1.33]. In subgroup analyses based on dose and duration of Lactobacillus supplementation, the pooled RRs for eradication rates were 1.36 (95% CI 1.15–1.60) in the high-dose group, 1.08 (95% CI 0.86–1.35) in the low-dose group, 1.24 (95% CI 1.06–1.46) in the long-term group, and 1.17 (95% CI 0.96–1.44) in the short-term group. With respect to side effects, Lactobacillus supplementation significantly reduced the incidence of diarrhea (RR = 0.30, 95% CI 0.10–0.85).

Conclusions: Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children. And a higher dose and a longer duration of supplementation may conduce to the positive impact of Lactobacillus on H. pylori eradication.

What is Known:

• Probiotics-supplemented triple therapy may be beneficial in improving H. pylori eradication rates and reducing therapy-related side effects in children. However, not all probiotics are beneficial to H. pylori eradication and the pooled outcomes based on different probiotics may be erroneously extrapolated to other ineffective strains.

What is New:

• Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

Abbreviations

CFU:

Colony-forming unit

CI:

Confidence interval

HpSA:

H. pylori stool antigen test

NSAID:

Nonsteroidal anti-inflammatory drug

RCT:

Randomized controlled trial

RR:

Relative risk

RUT:

Rapid urease test

PPI:

Proton pump inhibitor

UBT:

Urea breath test

References

  1. Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, Czinn S, Gold BD, Guarner J, Elitsur Y, Homan M, Kalach N, Kori M, Madrazo A, Megraud F, Papadopoulou A, Rowland M, ESPGHAN, NASPGHAN (2017) Joint ESPGHAN/NASPGHAN guidelines for the Management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr 64:991–1003. https://doi.org/10.1097/MPG.0000000000001594

    Article  PubMed  Google Scholar 

  2. Brito HS, Braga JA, Loggetto SR, Machado R, Granato CF, Kawakami E (2015) Helicobacter pylori infection and immune thrombocytopenic purpura in children and adolescents: a randomized controlled trial. Platelets 26:336–341. https://doi.org/10.3109/09537104.2014.911836

    Article  CAS  PubMed  Google Scholar 

  3. Gonzalez-Lopez MA, Velazquez-Guadarrama N, Romero-Espejel ME, Olivares-Trejo Jde J (2013) Helicobacter pylori secretes the chaperonin GroEL (HSP60) which binds iron. FEBS Lett 587:1823–1828. https://doi.org/10.1016/j.febslet.2013.04.048

    Article  CAS  PubMed  Google Scholar 

  4. Malfertheiner P, Megraud F, O'Morain CA et al (2017) Management of Helicobacter pylori infection the Maastricht V/Florence Consensus Report. Gut 66:6–30. https://doi.org/10.1136/gutjnl-2016-312288

    Article  CAS  PubMed  Google Scholar 

  5. Kalach N, Bontems P, Raymond J (2017) Helicobacter pylori infection in children. Helicobacter 22:e12414. https://doi.org/10.1111/hel.12414

    Article  Google Scholar 

  6. Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M, Hirschl AM, Andersen LP, Goossens H, Glupczynski Y (2013) Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 62:34–42. https://doi.org/10.1136/gutjnl-2012-302254

    Article  CAS  PubMed  Google Scholar 

  7. Bell GD, Powell K, Burridge SM, Pallecaros A, Jones PH, Gant PW, Harrison G, Trowell JE (1992) Experience with ‘triple’ anti-Helicobacter pylori eradication therapy: side effects and the importance of testing the pre-treatment bacterial isolate for metronidazole resistance. Aliment Pharmacol Ther 6:427–435

    Article  CAS  PubMed  Google Scholar 

  8. Molina-Infante J, Lucendo AJ, Angueira T, Rodriguez-Tellez M, Perez-Aisa A, Balboa A, Barrio J, Martin-Noguerol E, Gomez-Rodriguez BJ, Botargues-Bote JM, Gomez-Camarero J, Huerta A, Modolell I, Ariño I, Herranz-Bachiller MT, Bermejo F, McNicholl AG, O'Morain C, Gisbert JP, the European Registry on H. pylori management (Hp-EuReg) (2015) Optimised empiric triple and concomitant therapy for Helicobacter pylori eradication in clinical practice: the OPTRICON study. Alimet Pharmacol Ther 41:581–589. https://doi.org/10.1111/apt.13069

    Article  CAS  Google Scholar 

  9. Joint FAO/WHO Working Group (2002) Report on drafting guidelines for the evaluation of probiotics in food. Available at: www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf. Accessed 7 July 2018

  10. Li S, Huang XL, Sui JZ, Chen SY, Xie YT, Deng Y, Wang J, Xie L, Li TJ, He Y, Peng QL, Qin X, Zeng ZY (2014) Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children. Eur J Pediatr 173:153–161. https://doi.org/10.1007/s00431-013-2220-3

    Article  PubMed  Google Scholar 

  11. Szajewska H (2014) Pooling data on different probiotics is not appropriate to assess the efficacy of probiotics. Eur J Pediatr 173:975. https://doi.org/10.1007/s00431-014-2340-4

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yang YJ, Chuang CC, Yang HB, Lu CC, Sheu BS (2012) Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFkappaB pathways. BMC Microbiol 12:38. https://doi.org/10.1186/1471-2180-12-38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Myllyluoma E, Ahonen AM, Korpela R, Vapaatalo H, Kankuri E (2008) Effects of multispecies probiotic combination on Helicobacter pylori infection in vitro. Clin Vaccine Immunol 15:1472–1482. https://doi.org/10.1128/CVI.00080-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Francavilla R, Lionetti E, Castellaneta SP, Magistà AM, Maurogiovanni G, Bucci N, de Canio A, Indrio F, Cavallo L, Ierardi E, Miniello VL (2008) Inhibition of Helicobacter pylori infection in humans by Lactobacillus reuteri ATCC 55730 and effect on eradication therapy: a pilot study. Helicobacter 13:127–134. https://doi.org/10.1111/j.1523-5378.2008.00593.x

    Article  PubMed  Google Scholar 

  15. Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, Kalantzopoulos G, Tsakalidou E, Mentis A (2004) In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Appl Environ Microbiol 70:518–526. https://doi.org/10.1128/AEM.70.1.518-526.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA (2003) Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut 52:827–833. https://doi.org/10.1136/gut.52.6.827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Borruel N, Casellas F, Antolin M, Llopis M, Carol M, Espiin E, Naval J, Guarner F, Malagelada JR (2003) Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa. Am J Gastroenterol 98:865–870. https://doi.org/10.1111/j.1572-0241.2003.07384.x

    Article  CAS  PubMed  Google Scholar 

  18. Mukai T, Asasaka T, Sato E, Mori K, Matsumoto M, Ohori H (2002) Inhibition of binding of Helicobacter pylori to the glycolipid receptors by probiotic Lactobacillus reuteri. FEMS Immunol Med Microbiol 32:105–110

    Article  CAS  PubMed  Google Scholar 

  19. Lorca GL, Wadstrom T, Valdez GF, Ljungh A (2001) Lactobacillus acidophilus autolysins inhibit Helicobacter pylori in vitro. Curr Microbiol 42:39–44

    Article  CAS  PubMed  Google Scholar 

  20. Gotteland M, Cruchet S, Verbeke S (2001) Effect of Lactobacillus ingestion on the gastrointestinal mucosal barrier alterations induced by indometacin in humans. Aliment Pharmacol Ther 15:11–17

    Article  CAS  PubMed  Google Scholar 

  21. Marteau P, Minekus M, Havenaar R, Huisintveld JH (1997) Survival of lactic acid bacteria in a dynamic model of the stomach and small intestine: validation and the effects of bile. J Dairy Sci 80:1031–1037. https://doi.org/10.3168/jds.S0022-0302(97)76027-2

    Article  CAS  PubMed  Google Scholar 

  22. Bernet-Camard MF, Lievin V, Brassart D, Neeser JR, Servin AL, Hudault S (1997) The human Lactobacillus acidophilus strain LA1 secretes a nonbacteriocin antibacterial substance(s) active in vitro and in vivo. Appl Environ Microbiol 63:2747–2753

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Klaenhammer TR (1993) Genetics of bacteriocins produced by lactic acid bacteria. FEMS Microbiol Rev 12:39–85

    Article  CAS  PubMed  Google Scholar 

  24. Bhatia SJ, Kochar N, Abraham P, Nair NG, Metha AP (1989) Lactobacillus acidophilus inhibits growth of Campylobacter pylori in vitro. J Clin Microbiol 27:2328–2330

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Michetti P, Dorta G, Wiesel PH, Brassart D, Verdu E, Herranz M, Felley C, Porta N, Rouvet M, Blum AL, Corthésy-Theulaz I (1999) Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans. Digestion 60:203–209. https://doi.org/10.1159/000007660

    Article  CAS  PubMed  Google Scholar 

  26. Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions, version 5.1.0 (updated March 2011). The Cochrane Collaboration. Available at: www.handbook-5-1.cochrane.org/. Accessed 13 June 2018

  27. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–34. https://doi.org/10.1016/j.jclinepi.2009.06.006

    Article  PubMed  Google Scholar 

  28. Schunemann H, Brozek J, Guyatt G et al (2013) GRADE handbook for grading quality of evidence and strength of recommendations (Updated October 2013). The GRADE Working Group Available at: www.guidelinedevelopment.org/handbook

  29. Zhu XL, Liu Z, Wu ZQ, Li D, Jiang AP, Yu GX (2017) Clinical effects of different therapeutic regimens for Helicobacter pylori infection in children. Zhong Guo Dang Dai Er Ke Za Zhi 19:672–676. https://doi.org/10.7499/j.issn.1008-8830.2017.06.012

    Article  CAS  Google Scholar 

  30. Weiner N, Shaoul R (2015) Impact of age, gender, and addition of probiotics on treatment success for Helicobacter pylori in children. Glob Pediatr Health 2:1–4. https://doi.org/10.1177/2333794X15607798

    Article  Google Scholar 

  31. 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. https://doi.org/10.1186/1824-7288-38-63

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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 48:431–436. https://doi.org/10.1097/MPG.0b013e318182e716

    Article  CAS  PubMed  Google Scholar 

  33. Sykora J, Valeckova K, Amlerova J, Siala K, Dedek P, Watkins S, Varvarovska J, Stozicky F, Pazdiora P, Schwarz J (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 39:692–698

    Article  CAS  PubMed  Google Scholar 

  34. Shahraki T, Shahraki M, Shahri ES, Mohammadi M (2017) No significant impact of Lactobacillus reuteri on eradication of Helicobacter pylori in children (double-blind randomized clinical trial). Iran Red Crescent Med J 19:e42101

    Google Scholar 

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

    Google Scholar 

  36. Plewinska EM, Planeta-Malecka I, Bak-Romaniszyn L, Czkwianlanc E, Malecka-Panas E (2006) Probiotics in the treatment of Helicobacter pylori infection in children. Gastroenterol Pol 13(315–3):19

    Google Scholar 

  37. 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 23:79–84

    PubMed  Google Scholar 

  38. Graham DY, Fischbach L (2010) Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 59:1143–1153. https://doi.org/10.1136/gut.2009.192757

    Article  CAS  PubMed  Google Scholar 

  39. Zheng X, Lyu L, Mei Z (2013) Lactobacillus-containing probiotic supplementation increases Helicobacter pylori eradication rate: evidence from a meta-analysis. Rev Esp Enferm Dig 105:445–453. https://doi.org/10.4321/S1130-01082013000800002

    Article  PubMed  Google Scholar 

  40. Wang ZH, Gao QY, Fang JY (2013) Meta-analysis of the efficacy and safety of Lactobacillus-containing and Bifidobacterium-containing probiotic compound preparation in Helicobacter pylori eradication therapy. J Clin Gastroenterol 47:25–32. https://doi.org/10.1097/MCG.0b013e318266f6cf

    Article  PubMed  Google Scholar 

  41. Sheu BS, Wu JJ, Lo CY, Wu HW, Chen JH, Lin YS, Lin MD (2002) Impact of supplement with Lactobacillus and Bifidobacterium containing yogurt on triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther 16:1669–1675

    Article  PubMed  Google Scholar 

  42. Feng JR, Wang F, Qiu X, McFarland LV, Chen PF, Zhou R, Liu J, Zhao Q, Li J (2017) 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. https://doi.org/10.1007/s00228-017-2291-6

    Article  PubMed  Google Scholar 

  43. Zhang MM, Qian W, Qin YY, He J, Zhou YH (2015) Probiotics in Helicobacter pylori eradication therapy: a systematic review and meta-analysis. World J Gastroenterol 21:4345–4357. https://doi.org/10.3748/wjg.v21.i14.4345

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lv Z, Wang B, Zhou X, Wang F, Xie Y, Zheng H, Lv N (2015) Efficacy and safety of probiotics as adjuvant agents for Helicobacter pylori infection: a meta-analysis. Exp Ther Med 9:707–716. https://doi.org/10.3892/etm.2015.2174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lu M, Yu S, Deng J, Yan Q, Yang C, Xia G, Zhou X (2016) Efficacy of probiotic supplementation therapy for Helicobacter pylori eradication: a meta-analysis of randomized controlled trials. PLoS One 11:e0163743. https://doi.org/10.1371/journal.pone.0163743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Ministry of Eduaction Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children’s Hospital of Chongqing Medical University, No.136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China

    Hao-Ran Fang, Guo-Qiang Zhang & Zhong-Yue Li

  2. Department of Child Health Care, Children’s Hospital of Chongqing Medical University, Chongqing, China

    Jing-Yi Cheng

Authors
  1. Hao-Ran Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guo-Qiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing-Yi Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhong-Yue Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H-RF: study design, search and selection of articles, data extraction, statistical analysis, drafting the manuscript; G-QZ: data extraction, quality assessment, statistical analysis, revising the manuscript; J-YC: search and selection of articles, quality assessment, statistical analysis; Z-YL: study design, statistical analysis, drafting, and revising the manuscript.

Corresponding author

Correspondence to Zhong-Yue Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Not applicable for this manuscript.

Informed consent

Not applicable for this manuscript.

Additional information

Communicated by Peter de Winter

Electronic supplementary material

Table S1

(DOC 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fang, HR., Zhang, GQ., Cheng, JY. et al. Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials. Eur J Pediatr 178, 7–16 (2019). https://doi.org/10.1007/s00431-018-3282-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-018-3282-z

Keywords

Search

Navigation