Skip to main content

Effect of Saccharomyces boulardii CNCM I-745 as complementary treatment of Helicobacter pylori infection on gut microbiome

European Journal of Clinical Microbiology & Infectious Diseases volume 39, pages 1365–1372 (2020)Cite this article

Abstract

Conventional therapy for H. pylori infection includes the combination of antibiotics and a proton-pump inhibitor. Addition of probiotics as adjuvants for H. pylori antibiotic treatment can increase eradication rate and decrease treatment side effects. Although many studies show the benefits of S. boulardii CNCM I-745 in the treatment of H. pylori infection, the mechanism by which those benefits are achieved is unknown. Here, we report clinical characteristics and fecal microbiota changes comparing conventional anti-H. pylori therapy versus conventional therapy supplemented with S. boulardii CNCM I-745. A total of 74 patients were included in the current study; patients positive for H. pylori (n = 63) were randomly assigned to 2 groups: 34 patients received conventional therapy and 29 antibiotic therapy plus 750 mg of S. boulardii CNCM I-745 daily, for 2 weeks. Eleven patients negative for H. pylori infection were also studied. Patients provided 3 fecal samples: before initiating the antibiotic treatment, upon its completion, and 1 month after treatment. Patients were contacted every 72 h to inquire about side effects and compliance. DNA was extracted, and 16S rRNA was amplified and sequenced on Illumina MiSeq. Bioinformatic analysis was performed using QIIME2. Patients who received the probiotic had a significantly lower frequency of associated gastrointestinal symptoms (P = 0.028); higher number of bacterial diversity evenness (P = 0.0156); higher abundance of Enterobacteria; and lower abundance of Bacteroides and Clostridia upon treatment completion. Addition of S. boulardii CNCM I-745 induced a lower frequency of gastrointestinal symptoms that could be related to changes in gut microbiota.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386

    Article  CAS  PubMed  Google Scholar 

  2. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M et al (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 144(8):1941–1953

    CAS  PubMed  Google Scholar 

  3. IARC Helicobacter pylori Working Group. Helicobacter pylori eradication as a strategy for preventing gastric cancer. International Agency for Research on Cancer. Lyon, France; 2014. Report No.: 8

  4. Correa P, Piazuelo MB (2011) Helicobacter pylori infection and gastric adenocarcinoma. US Gastroenterol Hepatol Rev 7(1):59–64

    PubMed  PubMed Central  Google Scholar 

  5. György Miklós B (ed) Helicobacter pylori: a worldwide perspective 2014. Bentham Science Publishers, p 2014

  6. Egorov AI, Sempértegui F, Estrella B, Egas J, Naumova EN, Griffiths JK (2010) The effect of Helicobacter pylori infection on growth velocity in young children from poor urban communities in Ecuador. Int J Infect Dis 14(9):e788–e791

    PubMed  PubMed Central  Google Scholar 

  7. Gómez NA, Salvador A, Vargas PE, Zapatier JA, Alvarez J (2004) Seroprevalencia de Helicobacter pylori en la poblacion infantil Ecuatoriana [Seroprevalence of Helicobacter pylori among the child population of Ecuador]. Rev Gastroenterol Peru 24(3):230–233

    PubMed  Google Scholar 

  8. Salvador I, Mercado A, Bravo GL, Baldeón M, Fornasini M (2015) Risk and protective factors for gastric metaplasia and cancer: a hospital-based case-control study in Ecuador. Nutr Hosp 32(3):1193–1199

    PubMed  Google Scholar 

  9. Gyawali B, Kesselheim AS, D’Andrea E (2018) Does Helicobacter pylori eradication therapy to prevent gastric cancer increase all-cause mortality? Int J Cancer

  10. Fock KM, Graham DY, Malfertheiner P (2013) Helicobacter pylori research: historical insights and future directions. Nat Rev Gastroenterol Hepatol 10(8):495–500

    PubMed  PubMed Central  Google Scholar 

  11. Malfertheiner P, Sipponen P, Naumann M, Moayyedi P, Mégraud F, Xiao S-D et al (2005) Helicobacter pylori eradication has the potential to prevent gastric cancer: a state-of-the-art critique. Am J Gastroenterol 100(9):2100–2115

    PubMed  Google Scholar 

  12. Salama NR, Hartung ML, Müller A (2013) Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol 11(6):385–399

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S et al (2015) Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 64(9):1353–1367

    PubMed  Google Scholar 

  14. Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon ATR, Bazzoli F et al (2012) Management of Helicobacter pylori infection--the Maastricht IV/Florence Consensus Report. Gut. 61(5):646–664

    CAS  PubMed  Google Scholar 

  15. Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H et al (2010) Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter. 15(1):1–20

    CAS  PubMed  Google Scholar 

  16. Blaser MJ (2012) The Jeremiah Metzger Lecture: global warming redux: the disappearing microbiota and epidemic obesity. Trans Am Clin Climatol Assoc 123:230–238 discussion 239

    PubMed  PubMed Central  Google Scholar 

  17. Kyburz A, Fallegger A, Zhang X, Altobelli A, Artola-Boran M, Borbet T et al (2018) Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells. J Allergy Clin Immunol 19

  18. Dorer MS, Talarico S, Salama NR (2009) Helicobacter pylori’s unconventional role in health and disease. PLoS Pathog 5(10):e1000544

    PubMed  PubMed Central  Google Scholar 

  19. Chey WD, Leontiadis GI, Howden CW, Moss SF (2017) ACG clinical guideline: treatment of helicobacter pylori infection. Am J Gastroenterol 112(2):212–239

    PubMed  Google Scholar 

  20. Luther J, Higgins PDR, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD (2010) Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol 105(1):65–73

    PubMed  Google Scholar 

  21. Graham DY, Lee Y-C, Wu M-S (2014) Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol 12(2):177–86.e3 Discussion e12

    PubMed  Google Scholar 

  22. Graham DY, Lu H, Yamaoka Y (2007) A report card to grade Helicobacter pylori therapy. Helicobacter. 12(4):275–278

    PubMed  Google Scholar 

  23. Molina-Infante J, Lucendo AJ, Angueira T, Rodriguez-Tellez M, Perez-Aisa A, Balboa A et al (2015) Optimised empiric triple and concomitant therapy for Helicobacter pylori eradication in clinical practice: the OPTRICON study. Aliment Pharmacol Ther 41(6):581–589

    CAS  PubMed  Google Scholar 

  24. Zhu R, Chen K, Zheng Y-Y, Zhang H-W, Wang J-S, Xia Y-J et al (2014) Meta-analysis of the efficacy of probiotics in Helicobacter pylori eradication therapy. World J Gastroenterol 20(47):18013–18021

    PubMed  PubMed Central  Google Scholar 

  25. Li S, Huang X, Sui J, Chen S, Xie Y, Deng Y 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

    PubMed  Google Scholar 

  26. Ianiro G, Bruno G, Lopetuso L et al (2014) Role of yeasts in healthy and impaired gut microbiota: the gut mycome. Curr Pharm Des 20:4565. https://doi.org/10.2174/13816128113196660723

    Article  CAS  PubMed  Google Scholar 

  27. 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

    CAS  PubMed  Google Scholar 

  28. Zhang M-M, Qian W, Qin Y-Y, He J, Zhou Y-H (2015) Probiotics in Helicobacter pylori eradication therapy: a systematic review and meta-analysis. World J Gastroenterol 21(14):4345–4357

    PubMed  PubMed Central  Google Scholar 

  29. Sakarya S, Gunay N (2014) Saccharomyces boulardii expresses neuraminidase activity selective for α2,3-linked sialic acid that decreases Helicobacter pylori adhesion to host cells. APMIS. 122(10):941–950

    CAS  PubMed  Google Scholar 

  30. Wang Z-J, Chen X-F, Zhang Z-X, Li Y-C, Deng J, Tu J et al (2017) Effects of anti-Helicobacter pylori concomitant therapy and probiotic supplementation on the throat and gut microbiota in humans. Microb Pathog 109:156–161

    PubMed  Google Scholar 

  31. Yang L, Tian Z-B, Yu Y-N, Zhang C-P, Li X-Y, Mao T et al (2017) Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection. Pathog Dis 1:75(1)

    Google Scholar 

  32. Terciolo C, Dapoigny M, Andre F (2019) Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption. Clin Exp Gastroenterol 12:67–82

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hassan TMM, Al-Najjar SI, Al-Zahrani IH, Alanazi FIB, Alotibi MG (2016) Helicobacter pylori chronic gastritis updated Sydney grading in relation to endoscopic findings and H. pylori IgG antibody: diagnostic methods. J Microsc Ultrastruct 4(4):167–174

    PubMed  PubMed Central  Google Scholar 

  34. Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 26(19):2460–2461

    CAS  PubMed  Google Scholar 

  35. McDonald D, Price MN, Goodrich J, Nawrocki EP, DeSantis TZ, Probst A et al (2012) An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J 6(3):610–618

    CAS  PubMed  Google Scholar 

  36. DeSantis TZ, Hugenholtz P, Keller K, Brodie EL, Larsen N, Piceno YM et al (2006) NAST: a multiple sequence alignment server for comparative analysis of 16S rRNA genes. Nucleic Acids Res 34(Web Server issue):W394–W399

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Faith DP, Baker AM (2007) Phylogenetic diversity (PD) and biodiversity conservation: some bioinformatics challenges. Evol Bioinformatics Online 2:121–128

    Google Scholar 

  38. Jaccard P (1901) Etude comparative de la distribution florale dans une portion des Alpes et des Jura. Bulletin del la Société Vaudoise des Sciences Naturelles 37:547–579

    Google Scholar 

  39. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB et al (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A 110(22):9066–9071

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Mandal S, Van Treuren W, White RA, Eggesbø M, Knight R, Peddada SD (2015) Analysis of composition of microbiomes: a novel method for studying microbial composition. Microb Ecol Health Dis 26:27663

    PubMed  Google Scholar 

  41. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol 57(1):289–300

    Google Scholar 

  42. Zhao H-M, Ou-Yang H-J, Duan B-P, Xu B, Chen Z-Y, Tang J et al (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 

  43. Zojaji H, Ghobakhlou M, Rajabalinia H, Ataei E, Jahani Sherafat S, Moghimi-Dehkordi B et al (2013) The efficacy and safety of adding the probiotic Saccharomyces boulardiito standard triple therapy for eradication of H.pylori: a randomized controlled trial. Gastroenterol Hepatol Bed Bench 6(Suppl 1):S99–S104

    PubMed  PubMed Central  Google Scholar 

  44. Szajewska H, Kolodziej M (2015) Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Aliment Pharmacol Ther 42(7):793–801

    CAS  PubMed  Google Scholar 

  45. Seddik H, Boutallaka H, Elkoti I, Nejjari F, Berraida R, Berrag S et al (2019) Saccharomyces boulardii CNCM I-745 plus sequential therapy for Helicobacter pylori infections: a randomized, open-label trial. Eur J Clin Pharmacol 29

  46. Labus JS, Hsiao E, Tap J, Derrien M, Gupta A, Le Nevé B et al (2017) Clostridia from the gut microbiome are associated with brain functional connectivity and evoked symptoms in IBS. Gastroenterology. 152(5):S40

    Google Scholar 

  47. Lopetuso LR, Scaldaferri F, Petito V, Gasbarrini A (2013) Commensal clostridia: leading players in the maintenance of gut homeostasis. Gut Pathog 5(1):23

    PubMed  PubMed Central  Google Scholar 

  48. Sovran B, Planchais J, Jegou S, Straube M, Lamas B, Natividad JM et al (2018) Enterobacteriaceae are essential for the modulation of colitis severity by fungi. Microbiome. 6(1):152

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We also thank Dr. Eamonn Quigley and Francisco Guarner for the critical reading of the manuscript.

Funding

This study was partially funded by Universidad UTE, Universidad San Francisco de Quito (Fondos COCIBA), Universidad de Las Américas, and BioCodex (Gentilly, France).

Author information

Authors and Affiliations

  1. Instituto de Microbiología, COCIBA, Universidad San Francisco de Quito, Quito, Ecuador

    Paúl A. Cárdenas & Daniela Garcés

  2. Centro de Bioinformática, Universidad San Francisco de Quito, Quito, Ecuador

    Paúl A. Cárdenas & Belén Prado-Vivar

  3. Centro de Investigación Biomédica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador

    Nancy Flores, Marco Fornasini, Iván Salvador, Oswaldo Cargua & Manuel E. Baldeón

  4. Facultad de Medicina, Universidad de la República, Montevideo, Uruguay

    Henry Cohen

Authors
  1. Paúl A. Cárdenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Garcés
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Belén Prado-Vivar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nancy Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marco Fornasini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Henry Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Iván Salvador
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Oswaldo Cargua
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Manuel E. Baldeón
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: MEB, PC, MF, HC.

Data curation: MEB, PC, MF, DG, BP, NF.

Formal analysis: PC, MF, MEB.

Funding acquisition: HC, MEB, PC.

Investigation: IS, OC, MEB, PC, MF, DG, BP, NF.

Methodology: MEB, PC, MF, HC, IS, OC.

Project administration: MEB, PC, HC, MF.

Resources: MEB, PC, MF, IS, OC.

Software: PC, MF, MEB, DG.

Supervision: MEB, PC, HC, MF, NF.

Validation: MEB, PC, MF, DG, BP, NF, HC.

Visualization: PC, DG, BP, NF, MF, HC, IS, OC, MEB.

Writing – original draft: MEB, PC, MF.

Writing – review and editing: PC, DG, BP, NF, MF, HC, IS, OC, MEB.

Corresponding author

Correspondence to Paúl A. Cárdenas.

Ethics declarations

The human subjects Protection Committee at Universidad de Las Américas approved the study. Patients signed an informed consent form after receiving a full explanation of the research protocol to be included in the study.

Disclosure

Biocodex was not involved in study design, patient recruitment, and data analysis.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cárdenas, P., Garcés, D., Prado-Vivar, B. et al. Effect of Saccharomyces boulardii CNCM I-745 as complementary treatment of Helicobacter pylori infection on gut microbiome. Eur J Clin Microbiol Infect Dis 39, 1365–1372 (2020). https://doi.org/10.1007/s10096-020-03854-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-020-03854-3

Keywords

  • Saccharomyces boulardii CNCM I-745
  • Helicobacter pylori infection
  • Probiotics
  • Microbiome
  • Ecuador