Role of Probiotics in Eradication Therapy for Helicobacter pylori Infection

  • Shigeru KamiyaEmail author
  • Hideo Yonezawa
  • Takako Osaki
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1149)


Probiotics are defined as, “Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”, and have various effects including inhibitory capabilities on pathogens, stimulation of organ functions and activation of immune responses in the human. Probiotics were reported to inhibit Helicobacter pylori not only in vitro, but also in vivo studies. The mechanisms by which probiotics inhibit H. pylori infection include competition for nutrients, production of bactericidal substances, competitive inhibition of adherence and stimulation of host functions and immunity. In addition, probiotics are clinically used for eradication therapy of H. pylori infection, and the effects of probiotics as single treatment and combination use with other drugs including proton pump inhibitors and antibiotics against H. pylori are reported. It has been testified that probiotics increase the eradication rate and prevent adverse events including diarrhea, nausea, vomiting and taste disorder. In the Maastrich V/Florence Consensus Report 2017, it was stated that some probiotics may have a beneficial effect on H. pylori eradication and are effective in reducing side effects of eradication therapy, but more research is needed to answer several questions concerning the mechanisms of probiotics action. In addition, strain specificity, dosages and duration times of probiotics used for H. pylori eradication therapy need to be clarified in future studies.


H. pylori Probiotics Microbiota Eradication therapy Adverse event 


  1. Aiba Y, Suzuki N, Kabir AM, Takagi A, Koga Y (1998) Lactic acid-mediated suppression of Helicobacter pylori by the oral administration of Lactobacillus salivarius as a probiotic in a gnotobiotic murine model. Am J Gastroenterol 93:2097–2101. Scholar
  2. Armuzzi A, Cremonini F, Bartolozzi F, Canducci F, Candelli M, Ojetti V, Cammarota G, Anti M, De L, Pola P, Gasbarrini G, Gasbarrini A (2001) The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy. Alimen Pharmacol Ther 15:163–169CrossRefGoogle Scholar
  3. Bergonzelli GE, Granato D, Pridmore RD, Marvin-Guy LF, Donnicola D, Corthesy-Theulaz IE (2006) GroEL of Lactobacillus johnsonii La1 (NCC533) is cell surface associated: potential role in interactions with the host and the gastric pathogen Helicobacter pylori. Infect Immun 74:425–434. Scholar
  4. Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG (2008) Dutch Acute Pancreatitis Study Group: probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371:651–659. Scholar
  5. Boonyaritichaikij S, Kuwabara K, Nagano J, Kobayashi K, Koga Y (2009) Long-term administration of probiotics to asymptomatic pre-school children for either eradication or the prevention of Helicobacter pylori infection. Helicobacter 14:202–207. Scholar
  6. Canducci F, Armuzzi A, Cremonini F, Cammarota G, Bartolozzi F, Pola P, Gasbarrini G, Gasbarrini A (2000) A lyophilized inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates. Aliment Pharmacol Ther 14:1625–1629CrossRefGoogle Scholar
  7. Cremonini F, Di Caro S, Covino M, Armuzzi A, Gabrielli M, Santarelli L, Nista EC, Cammarota G, Gasbarrini G, Gasbarrini A (2002) Effect of different probiotic preparations on anti-Helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol 97:2744–2749. Scholar
  8. Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, Jones NL, Render C, Leontiadis GI, Moayyedi P, Marshall JK (2016) The Tronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 151:51–69. Scholar
  9. 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. Scholar
  10. Felley CP, Corthesy-Theulaz I, Rivero JL, Sipponen P, Kaufmann M, Bauerfeind P, Wiesel PH, Brassart D, Pfeifer A, Blum AL, Michetti P (2001) Favourable effect of an acididied mild (LC-1) on Helicobacter pylori gastritis in man. Eur J Gastroenterol Hepatol 13:25–29CrossRefGoogle Scholar
  11. Galdeano CM, Perdigon G (2006) The probiotic bacterium Lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clin Vaccine Immunol 13:219–226. Scholar
  12. Goderska K, Agudo Pena S, Alarcon T (2018) Helicobacter pylori treatment: antibiotics or probiotics. Appl Microbiol Biotechnol 102:1–7. Scholar
  13. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME (2014) The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11:506–514. Scholar
  14. Hoarau C, Martin L, Faugaret D, Baron C, Dauba A, Aubert-Jacauin C, Velge-Roussel F, Lebranchu Y (2008) Supernatant from Bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells. PLoS One 3:e2753. Scholar
  15. Jarosz M, Rychlik E, Siuba M, REspondek W, Ryzko-Skiba M, Sajor I, Gugala S, Blazejczyk T, Ciok J (2009) Dietary and socio-economic factors in relation to Helicobacter pylori re-infection. World J Gastroenterol 15:1119–1125CrossRefGoogle Scholar
  16. Johnson-Henry KC, Mitchell DJ, Avitzur Y, Galindo-Mata E, Jones NL, Sherman PM (2004) Probiotics reduce bacterial colonization and gastric inflammation in H. pylori-infected mice. Dig Dis Sci 49:1095–1102CrossRefGoogle Scholar
  17. Jung JH, Cho IK, Lee CH, Song GG, Lim JH (2018) Clinical outcomes of standard triple therapy plus probiotics or concomitant therapy for Helicobacter pylori infection. Gut Liver 12:165–172. Scholar
  18. Kabir AM, Aiba Y, Takagi A, Kamiya S, Miwa T, Koga Y (1997) Prevention of Helicobacter pylori by lactobacilli in a gnotobiotic murine model. Gut 41:49–55CrossRefGoogle Scholar
  19. Kamiya S (2011) Effect of probiotics on intestinal infections. Intestinal Res 9:171–178CrossRefGoogle Scholar
  20. Kim JM, Kim JS, Kim YJ, Oh YK, Kim IY, Chee YJ, Han JS, Jung HC (2008a) Conjugated linoleic acids produced by Lactobacillus dissociates IKK-γ and Hsp90 complex in Helicobacter pylori-infected gastric epithelial cells. Lab Investig 88:541–552. Scholar
  21. Kim MN, Kim N, Lee SH, Park YS, Hwang JH, Kim JW, Jeong SH, Lee DH, Kim JS, Jung HC, Song IS (2008b) The effects of probiotics on PPI-triple therapy for Helicobacter pylori eradication. Helicobacter 13:261–268. Scholar
  22. Lesbros-Pantoflickova D, Corthesy-Theulaz I, Blum AL (2007) Helicobacter pylori and probiotics. J Nutr 137(Suppl 2):S812–S818. Scholar
  23. Lin WH, Lin CK, Sheu SJ, Hwang CF, Ye WT, Hwang WZ, Tsen HY (2009) Antagonistic activity of spent culture supernatants of lactic acid bacteria against Helicobacter pylori growth and infection in human gastric epithelial AGS cells. J Food Sci 74:225–230. Scholar
  24. Linsalata M, Russo F, Berloco P, Caruso ML, Matteo GD, Cifone MG, Simone CD, Ierardi E, Di Leo A (2004) The influence of Lactobacillus brevis on ornithine decarboxylase activity and polyamine profiles in Helicobacter pylori-infected gastric mucosa. Helicobacter 9:165–172. Scholar
  25. Lopez-Brea M, Alarcon T, Domingo D, Diaz-Reganon J (2008) Inhibitory effect of gram-negative and gram-positive microorganisms against Helicobacter pylori. J Antimicrob Chemother 61:139–142. Scholar
  26. Losurdo G, Cubisino R, Barone M, Principi M, Leandro G, Ierardi E, Di Leo A (2018) Probiotic monotherapy and Helicobacter pylori eradication: a systemic review with pooled-data analysis. World J Gastroenterol 24:139–149. Scholar
  27. Lu C, Sang J, He H, Wan X, Lin Y, Li L, Li Y, Yu C (2016) Probiotic supplementation does not improve eradication rate of Helicobacter pylori infection compared to placebo based on standard therapy: a meta-analysis. Sci Rep 6:23522/DOI 10.1038. Scholar
  28. Lü 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(10):1371. Scholar
  29. Malferltheiner P, Megraud F, O’Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM, on behalf of the European Helicobacter and Microbiota Study Group and Consensus panel (2017) Management of Helicobacter pylori infection – the Maastrich V/Florence Consensus Report. Gut 66:6–30. Scholar
  30. McFarland LV, Huang Y, Wang L, Malfertheiner P (2016) Systematic review and meta-analysis: multi-strain probiotics as a adjunct therapy for Helicobacter pylori eradication and prevention of adverse effects. United European Gastroenterol J 4:546–561. Scholar
  31. Michetti P, Dorta G, Wiesel H, Brassart D, Verdu E, Herranz M, Felley C, Porta N, Rouvet M, Blum AL, Corthesy-Theulaz I (1999) Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans. Digestion 60:203–209. Scholar
  32. Nam H, Ha M, Bae O, Lee Y (2002) Effect of Weissella confusa strain PL9001 on the adherence and growth of Hellicobacter pylori. Appl Environ Microbiol 68:4642–4645CrossRefGoogle Scholar
  33. Nista EC, Candelli M, Cremonini F, Cazzato IA, Zocco MA, Franceschi F, Cammarota G, Gasbarrini G, Gasbarrini A (2004) Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: ranmdomized, double-blind, placebo controlled trial. Aliment Pharmacol Ther 20:1181–1188. Scholar
  34. Pandey KR, Naik SR, Vakil BV (2015) Probiotics, prebiotics and synbiotics – a review. J Food Sci Technol 52:7577–7587. Scholar
  35. Patel R, Cockerill FR, Porayko MK, Osmon DR, Ilstrup DR, Keating MR (1994) Lactobacillemia in liver transplant patients. Clin Infect Dis 18:207–212CrossRefGoogle Scholar
  36. Pinchuk IV, Bressollier P, Verneuil B, Fenet B, Sorokulova IB, Megraud F, Urdaci MC (2001) In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics. Antimicrob Agents Chemother 45:3156–3161. Scholar
  37. Pletincx M, Legein J, Vandenplas Y (1995) Fungemia with Saccharomyces boulardii in a 1-year-old girl with protracted diarrhea. J Pediatr Gastroenterol Nutr 21:113–115CrossRefGoogle Scholar
  38. Quigley EM (2010) Prebiotics and probiotics: modifying and mining the microbiota. Pharmacol Res 61:213–218. Scholar
  39. Rosania R, Minenna MF, Giorgio F, Facciorusso A, De Francesco V, Hassan C, Panella C, Ierardi E (2012) Probiotic multistrain treatment may eradicate Helicobacter pylori from the stomach of dyspeptics; a placebo-controlled pilot study. Inflamm Allergy Drug Targets 11:244–249CrossRefGoogle Scholar
  40. Sakamoto I, Igarashi M, Kimura K, Takagi A, Miwa T, Koga Y (2001) Suppresive effect of Lactobacillus gasseri OLL 2716 (LG21) on Helicobacter pylori infection in humans. J Antimicrob Chemother 47:709–710CrossRefGoogle Scholar
  41. 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 Shirota. Appl Environ Microbiol 70:518–526CrossRefGoogle Scholar
  42. Sachdeva A, Nagpal J (2009) Effect of fermented milk-based probiotic preparations on Helicobacter pylori eradication: a systemic review and meta-analysis of randomized-controlled trials. Eur J Gatrotenterol Hepatol 21:45–53. Scholar
  43. 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 16:1669–1675CrossRefGoogle Scholar
  44. Sirvan BN, Usta MK, Kizikan NU, Urganci N (2017) Are synbiotics added to the standard therapy to eradicate Helicobacter pylori in children beneficial? A randomized controlled study. Eur J Hepatogastroenterol 7:17–22. Scholar
  45. Tannock GW (1999) Identification of lactobacilli and bifidobacteria. Curr Issues Mol Biol 1:53–64PubMedGoogle Scholar
  46. Takahashi M, Taguchi H, Yamaguchi H, Osaki T, Kamiya S (2000) Studies of the effect of Clostridium butyricum on Helicobacter pylori in several test models including gnotobiotic mice. J Med Microbiol 49:635–642. Scholar
  47. Techo S, Visseanguan W, Vilaichone R-k, Tanasupawat S (2018) Characterization and antibacterial activity against Helicobacter pylori of lactic acid bacteria isolated from Thai fermented rice noodle. Probiotics Antimicrob Proteins. Scholar
  48. Thomas DW, Greer FR, American Academy of Pediatrics Committee on Nutrition, American Academy of Pediatrics Section on Gastroenterology, Hepatology and Nutrition (2010) Probiotics and prebiotics in pediatrics. Pediatrics 126:1217–1231. Scholar
  49. Tong JL, Ran ZH, Shen J, Zhang CX, Xiao SD (2007) Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse effects during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther 25:155–168. Scholar
  50. Urrutia-Beca VH, Escamilla-Garcia E, de la Garza-Ramos MA, Tamez-Guerra P, Gomez-Flores R, Urbina-Rios CS (2018) In vitro antimicrobial activity and downregulation of virulence gene expression on Helicobacter pylori by reuterin. Probiotics Antimicrob Proteins 10:168–175. Scholar
  51. Wang F, Feng J, Chen P, Liu X, Ma M, Zhou R, Chang Y, Liu J, Li J, Zhao Q (2017) Probiotics in Helicobacter pylori eradication therapy: systemic review and network meta-analysis. Clin Res Hepatol Gastroenterol 41:466–475. Scholar
  52. Wang KY, Li SN, Liu CS, Perng DS, Su YC, Wu DC, Jan CM, Lai CH, Wang TN, Wang WM (2004) Effects of ingesting Lactobacillus- and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori. Am J Clin Nutr 80:737–741. Scholar
  53. Wen J, Peng P, Chen P, Zeng L, Pan Q, Wei W, He J (2017) Probiotics in 14-day triple therapy for Asian pediatric patients with Helicobacter pylori infection: a network meta-analysis. Oncotarget 8:96406–96418. Scholar
  54. Zagari RM, Ramano M, Ojetti SR, Gullini S, Annibale B, Farianti F, Ieraudi E, Maconi G, Rugge M, Calabrese C, Di Mario F, Luzza F, Pretolani S, Savio A, Gasbarrini G, Caselli M (2015) Guidelines for the management of Helicobacter pylori infection in Italy: the III Working Group Consensus Report 2015. Dig Liv Dis 47:903–912. Scholar
  55. Zhao K, Xie Q, Xu D, Guo Y, Tao X, Wei H, Wan C (2018) Antagonistics of Lactobacillus plantarum ZDY2013 against Helicobacter pylori SS1 and its infection in vitro in human gastric epithelial AGS cells. J Biosci Bioeng 126:458–463. Scholar
  56. Zhou C, Ma FZ, Deng XJ, Yuan H, Ma HS (2008) Lactobacillus inhibit interleukin-8 production induced by Helicobacter pylori. World J Gastroenterol 14:5090–5095CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Faculty of Health SciencesKyorin UniversityTokyoJapan
  2. 2.Department of Infectious DiseasesKyorin University School of MedicineTokyoJapan

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