Efficacy of Lactobacillus-supplemented triple therapy for H. pylori eradication: A meta-analysis of randomized controlled trials

Autoři: Mingyang Yu aff001;  Rongguang Zhang aff001;  Peng Ni aff001;  Shuaiyin Chen aff001;  Guangcai Duan aff001
Působiště autorů: Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223309



To assess the effect of Lactobacillus supplementation on Helicobacter pylori eradication rates and side effects of the triple therapy.


PubMed, Embase, Web of Science and Cochrane Library were searched for articles published up to July, 2019. Review Manager 5.3 and Stata 12.0 were used for statistical analyses.


The initial database search resulted in 852 articles. Through exclusion and screening, 11 randomized controlled trials involving a total of 724 patients were finally included in this meta-analysis. The H. pylori elimination rate in the Lactobacillus supplement group was significantly higher than that in the control group (RR 1.16, 95% CI 1.08–1.25, P<0.0001). Subgroup analysis showed that the eradication rates were significantly enhanced in both adults and children group, and no significant difference was detected between Asia and Europe group. In addition, sub-analysis based on duration of Lactobacillus supplementation showed the pooled RRs in the long-term and short-term groups were 1.17 (95%CI 1.06–1.30) and 1.16 (95% CI 1.04–1.30), respectively. Regarding the Lactobacillus strains, the pooled RR was 1.33 (95% CI 1.10–1.62) in the L. casei group, 1.18 (95% CI 1.03–1.34) in the L. reuteri group while 1.02 (95% CI 0.87–1.21) in the Lactobacillus GG group. As for the total side effects, Lactobacillus supplementation significantly reduced the incidence of taste disturbance (RR = 0.36, 95% CI 0.17–0.74, P = 0.005).


Lactobacillus supplementation during the treatment of Helicobacter pylori infection can effectively improve the eradication rates, and reduce the incidence of therapy-related taste disturbance.

Klíčová slova:

Antibiotics – Database searching – Gastrointestinal infections – Helicobacter pylori – Histology – Lactobacillus – Probiotics


1. Chen C, Mao Y, Du J, Xu Y, Zhu Z, Cao H. Helicobacter pylori infection associated with an increased risk of colorectal adenomatous polyps in the Chinese population. BMC Gastroenterol. 2019; 19 (1): 14. doi: 10.1186/s12876-018-0918-4 30665367

2. Wang F, Meng W, Wang B, Qiao L. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett. 2014; 345 (2): 196–202. doi: 10.1016/j.canlet.2013.08.016 23981572

3. Jarosz M, Rychlik E, Siuba M, Respondek W, Ryzko-Skiba M, Sajór I, et al. Dietary and socio-economic factors in relation to Helicobacter pylori re-infection. World J Gastroenterol. 2009; 15 (9): 1119–25. doi: 10.3748/wjg.15.1119 19266606

4. Fallone CA, Chiba N, Fischbach L, Zanten SV, Gisbert JP, Hunt RH, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016; 151 (1): 51–69. doi: 10.1053/j.gastro.2016.04.006 27102658

5. Yang JC, Lu CW, Lin CJ. Treatment of Helicobacter pylori infection: current status and future concepts. World J Gastroenterol. 2014; 20 (18): 5283–93. doi: 10.3748/wjg.v20.i18.5283 24833858

6. Vitor JMB, Vale FF. Alternative therapies for Helicobacter pylori:probiotics and phytomedicine. FEMS Immunol Med Microbiol. 2011; 63: 153–64. doi: 10.1111/j.1574-695X.2011.00865.x 22077218

7. García A, Sáez K, Delgado C, González CL. Low co-existence rates of Lactobacillus spp, and Helicobacter pylori detected in gastric biopsies from patients with gastrointestinal symptoms. Rev Esp Enferm Dig. 2012;104:473–8. doi: 10.4321/s1130-01082012000900005 23130855

8. Mégraud F. Antibiotic resistance is the key element in treatment of Helicobacter pylori infection. Gastroenterology. 2018; 155 (5): 1300–2. doi: 10.1053/j.gastro.2018.10.012 30308190

9. Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut. 2010; 59 (8): 1143–53. doi: 10.1136/gut.2009.192757 20525969

10. Parker EA, Roy T, D'Adamo CR, Wieland LS. Probiotics and gastrointestinal conditions: An overview of evidence from the Cochrane Collaboration. Nutrition. 2018; 45: 125–34. doi: 10.1016/j.nut.2017.06.024 28870406

11. Gotteland M, Brunser O, Cruchet S. Systematic review: are probiotics useful in controlling gastric colonization by Helicobacter pylori? Aliment Pharmacol Ther. 2006; 23 (8): 1077–86. doi: 10.1111/j.1365-2036.2006.02868.x 16611267

12. Wang YH, Huang Y. 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. 2014; 30:847–53. doi: 10.1007/s11274-013-1490-2 24233772

13. Shavakhi A, Ahmad S, Tabesh E, Yaghoutkar A, Hashemi H, Tabesh F, et al. The effects of multistrain probiotic compound on bismuth-containing quadruple therapy for Helicobacter pylori infection: a randomized placebo-controlled triple-blind study. Helicobacter. 2013; 18:280–84. doi: 10.1111/hel.12047 23433200

14. Szajewska H. Pooling data on different probiotics is not appropriate to assess the efficacy of probiotics. Eur J Pediatr. 2014; 173 (7): 975. doi: 10.1007/s00431-014-2340-4 24849615

15. Sgouras D, Maragkoudakis P, Petraki K, Eriotou E, Michopoulos S, Kalantzopoulos G, et al. In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Appl Environ Microbiol. 2004; 70 (1): 518–26. doi: 10.1128/AEM.70.1.518-526.2004 14711683

16. Yang YJ, Chuang CC, Yang HB, Lu CC, Sheu BS. Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFkappaB pathways. BMC Microbiol. 2012; 12: 38. doi: 10.1186/1471-2180-12-38 22429929

17. Lorca GL, Wadström T, Valdez GF, Ljungh A. Lactobacillus acidophilus autolysins inhibit Helicobacter pylori in vitro. Curr Microbiol. 2001; 42 (1): 39–44. 11116395

18. Isobe H, Nishiyama A, Takano T, Higuchi W, Nakagawa S, Taneike I, et al. Reduction of overall Helicobacter pylori colonization levels in the stomach of Mongolian gerbil by Lactobacillus johnsonii La1 (LC1) and its in vitro activities against H. pylori motility and adherence. Biosci Biotechnol Biochem. 2012; 76 (4): 850–52. doi: 10.1271/bbb.110921 22484956

19. Cui Y, Wang CL, Liu XW, Wang XH, Chen LL, Zhao X et al. Two stomach-originated Lactobacillus strains improve Helicobacter pylori infected murine gastritis. World J Gastroenterol. 2010; 16 (4): 445–52. doi: 10.3748/wjg.v16.i4.445 20101769

20. Shi X, Zhang J, Mo L, Shi J, Qin M, Huang X. Efficacy and safety of probiotics in eradicating Helicobacter pylori: A network meta-analysis. Medicine. 2019; 98(15): e15180. doi: 10.1097/MD.0000000000015180 30985706

21. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration. 2011.

22. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009; 62 (10): 1–34. doi: 10.1016/j.jclinepi.2009.06.006 19631507

23. Schunemann H, Brozek J, Guyatt G. GRADE handbook for grading quality of evidence and strength of recommendations (updated October 2013). The GRADE Working Group. 2013.

24. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analysis. BMJ. 2003; 327: 557–60. doi: 10.1136/bmj.327.7414.557 12958120

25. DerSimonian R, Laird N. Meta-analysis in clinical trails. Control Clin Trails. 1986; 7: 177–88. 3802833

26. Deguchi R, Nakaminami H, Rimbara E, Noguchi N, Sasatsu M, Suzuki T, et al. Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy. J Gastroen Hepatol. 2011; 27 (5): 888–92. doi: 10.1111/j.1440-1746.2011.06985.x 22098133

27. Sýkora J, Valecková K, Amlerová J, Siala K, Dedek P, Watkins S, et al. 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. 2005; 39 (8): 692–98. doi: 10.1097/01.mcg.0000173855.77191.44 16082279

28. José E, Sahagún F, Mónica S, et al. Erradicación de Helicobacter pylori: esquema triple tradicional versus mismo esquema más probiótico. Cirugía y Cirujanos. 2007; 75 (5): 333–6. 18158878

29. Medeiros JA, Gonçalves TM, Boyanova L, Pereira MI, Pereira AM, Cabrita AM, et al. Evaluation of Helicobacter pylori eradication by triple therapy plus Lactobacillus acidophilus compared to triple therapy alone. Eur J Clin Microbiol. 2011; 30 (4): 555–59. doi: 10.1007/s10096-010-1119-4 21207091

30. Ojetti V, Bruno G, Ainora ME, Gigante G, Rizzo G, Roccarina D, et al. Impact of Lactobacillus reuteri Supplementation on anti-Helicobacter pylori levofloxacin-based second-line therapy. Gastroent Res Pract. 2012; 2012: 1–6. doi: 10.1155/2012/740381 22690211

31. Emara MH, Mohamed SY, Abdel-Aziz HR. Lactobacillus reuteri in management of Helicobacter pylori infection in dyspeptic patients: a double-blind placebo-controlled randomized clinical trial. Ther Advin Gastroenter. 2014; 7 (1): 4–13. doi: 10.1177/1756283X13503514 24381643

32. Shahraki T, Shahraki M, Shahri E, et al. No significant impact of Lactobacillus reuteri on eradication of Helicobacter pylori in children (double-blind randomized clinical trial). IRAN Red Crescent. 2017; 19: 421. doi: 10.5812/ircmj.42101

33. Szajewska H, Albrecht Y, Topczewska-Cabanek Z. 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 Gastr Nutr. 2009; 48 (4): 431–6. doi: 10.1097/mpg.0b013e318182e716 19330931

34. Francavilla R, Polimeno L, Demichina A, Maurogiovanni G, Principi B, Scaccianoce G, et al. Lactobacillus reuteri strain combination in Helicobacter pylori infection: a randomized, double-blind, placebo-controlled study. J Clin Gastroenterol. 2014; 48 (5):407–13. doi: 10.1097/MCG.0000000000000007 24296423

35. Armuzzi A, Cremonini F, Ojetti V, Bartolozzi F, Canducci F, Candelli M, et al. Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study. Digestion. 2001; 63 (1):1–7. doi: 10.1159/000051865 11173893

36. Lionetti E, Miniello VL, Castellaneta SP, Magistá AM, Canio A, Maurogiovanni G, et al. Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomized placebo controlled trial. Aliment Pharmacol Ther. 2006; 15 24 (10): 1461–8. doi: 10.1111/j.1365-2036.2006.03145.x 17032283

37. Coconnier MH, Lievin V, Hemery E, Servin AL. Antagonistic activity against Helicobacter infection in vitro and in vivo by the human Lactobacillus acidophilus strain LB. Appl Environ Microbiol. 1998; 64 (11): 4573–80. 9797324

38. Sung M, Lim. Anti-Helicobacter pylori activity of antimicrobial substances produced by lactic acid bacteria isolated from Baikkimchi. Applied Biological Chemistry. 2014; 57 (5): 621–30. doi: 10.1007/s13765-014-4198-6

39. Francavilla R, Lionetti E, Castellaneta SP, Magistà AM, Maurogiovanni G, Bucci N, et al. Inhibition of Helicobacter pylori infection in humans by Lactobacillus reuteri ATCC 55730 and effect on eradication therapy: a pilot study. Helicobacter. 2008; 13 (2): 127–34. doi: 10.1111/j.1523-5378.2008.00593.x 18321302

40. Mukai T, Asasaka T, Sato E, Mori K, Matsumoto M, Ohori H. Inhibition of binding of Helicobacter pylori to the glycolipid receptors by probiotic Lactobacillus reuteri. FEMS Immunol Med Microbiol. 2002; 32 (2): 105–10. doi: 10.1111/j.1574-695X.2002.tb00541.x 11821231

41. Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003; 52 (6): 827–33. doi: 10.1136/gut.52.6.827 12740338

42. Myllyluoma E, Ahonen AM, Korpela R, Vapaatalo H, Kankuri E. Effects of multispecies probiotic combination on Helicobacter pylori infection in vitro. Clin Vaccine Immunol. 2008; 15 (9): 1472–82. doi: 10.1128/CVI.00080-08 18579692

43. Rousseaux C, Thuru X, Gelot A, Barnich N, Neut C, Dubuquoy L, et al. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med. 2007; 13 (1): 35–7. doi: 10.1038/nm1521 17159985

44. Zheng X, Yu L, Mei Z. Lactobacillus-containing probiotic supplementation increases Helicobacter pylori eradication rate: evidence from a meta-analysis. Rev Esp Enferm Dig. 2013; 105 (8): 445–53. doi: 10.4321/s1130-01082013000800002 24274441

45. Wang ZH, Gao QY, Fang JY. Meta-analysis of the efficacy and safety of Lactobacillus-containing and Bifidobacterium-containing probiotic compound preparation in Helicobacter pylori eradication therapy. J Clin Gastroenterol. 2013; 47 (1): 25–32. doi: 10.1097/MCG.0b013e318266f6cf 23090045

46. Fang HR, Zhang GQ, Cheng JY, Li ZY. Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials. Eur J Pediatr. 2019; 178 (1): 7–16. doi: 10.1007/s00431-018-3282-z 30446816

47. Feng JR, Wang F, Qiu X, McFarland LV, Chen PF, Zhou R, 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. 2017; 73(10):1199–208. doi: 10.1007/s00228-017-2291-6 28681177

48. Cindoruk M, Erkan G, Karakan T, Dursun A, Unal S. Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: a prospective randomized placebo-controlled double-blind study. Helicobacter. 2007; 12 (4):309–16. doi: 10.1111/j.1523-5378.2007.00516.x 17669103

49. Hurduc V, Plesca D, Dragomir D, Sajin M, Vandenplas Y. A randomized, open trial evaluating the effect of Saccharomyces boulardii on the eradication rate of Helicobacter pylori infection in children. Acta Paediatr. 2009; 98(1):127–31. doi: 10.1111/j.1651-2227.2008.00977.x 18681892

50. Cremonini F, Di Caro S, Covino M, Armuzzi A, Gabrielli M, Santarelli L, et al. Effect of different probiotic preparations on anti-helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol. 2002; 97(11):2744–9. doi: 10.1111/j.1572-0241.2002.07063.x 12425542

51. Lv Z, Wang B, Zhou X, Wang F, Xie Y, Zheng H, et al. Efficacy and safety of probiotics as adjuvant agents for Helicobacter pylori infection: A meta-analysis. Exp Ther Med. 2015; 9 (3):707–16. doi: 10.3892/etm.2015.2174 25667617

52. Li S, Huang XL, Sui JZ, Chen SY, Xie YT, Deng Y, et al. Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children. Eur J Pediatr. 2014; 173 (2):153–61. doi: 10.1007/s00431-013-2220-3 24323343

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