Skip to main content

Advertisement

Log in

Probiotic Saccharomyces cerevisiae strains as biotherapeutic tools: is there room for improvement?

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

The probiotic yeast Saccharomyces cerevisiae var boulardii is widely used as a low cost and efficient adjuvant against gastrointestinal tract disorders such as inflammatory bowel disease and treatment of several types of diarrhea, both in humans and animals. S. boulardii exerts its protective mechanisms by binding and neutralizing enteric pathogens or their toxins, by reducing inflammation and by inducing the secretion of sIgA. Although several S. cerevisiae strains have proven probiotic potential in both humans and animals, only S. boulardii is currently licensed for use in humans. Recently, some researchers started using S. boulardii as heterologous protein expression systems. Combined with their probiotic activity, the use of these strains as prophylactic and therapeutic proteins carriers might result in a positive combined effort to fight specific diseases. Here, we provide an overview of the current use of S. cerevisiae strains as probiotics and their mechanisms of action. We also discuss their potential to produce molecules with biotherapeutic application and the advantages and hurdles of this approach. Finally, we suggest future directions and alternatives for which the combined effort of specific immunomodulatory effects of probiotic S. cerevisiae strains and ability to express desired foreign genes would find a practical application.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ardiani A, Higgins JP, Hodge JW (2010) Vaccines based on whole recombinant Saccharomyces cerevisiae cells. FEMS Yeast Res 10:1060–1069

    Article  CAS  PubMed  Google Scholar 

  • Batista TM, Marques ETA, Franco GR, Douradinha B (2014) Draft genome sequence of the probiotic yeast Saccharomyces cerevisiae var boulardii strain ATCC MYA-796. Genome Announc 2:e01345–14

    PubMed Central  PubMed  Google Scholar 

  • Brandão RL, Castro IM, Bambirra EA, Amaral C, Fietto LG, Tropia MJM, José M, Dos Santos RG, Gomes NCM, Nicoli R, Amaral SC, Jose M (1998) Intracellular signal triggered by cholera toxin in Saccharomyces boulardii and Saccharomyces cerevisiae. Appl Env Microbiol 64:564–568

    Google Scholar 

  • Buts J-P, De Keyser N (2006) Effects of Saccharomyces boulardii on intestinal mucosa. Dig Dis Sci 51:1485–1492. doi:10.1007/s10620-005-9016-x

    Article  PubMed  Google Scholar 

  • Byrd J, Bresalier R (2004) Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev 23:77–99

    Article  CAS  PubMed  Google Scholar 

  • Cummins J, Ho M-W (2005) Genetically modified probiotics should be banned. Microb Ecol Heal Dis 17:66–68. doi:10.1080/08910600510044480

    Article  Google Scholar 

  • Czerucka D, Piche T, Rampal P (2007) Review article: yeast as probiotics—Saccharomyces boulardii. Aliment Pharmacol Ther 26:767–778

    Article  CAS  PubMed  Google Scholar 

  • Da Silva NA, Srikrishnan S (2012) Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae. FEMS Yeast Res 12:197–214

    Article  PubMed  Google Scholar 

  • Dalmasso G, Loubat A, Dahan S, Calle G, Rampal P, Czerucka D (2006) Saccharomyces boulardii prevents TNF-alpha-induced apoptosis in EHEC-infected T84 cells. Res Microbiol 157:456–465. doi:10.1016/j.resmic.2005.11.007

    Article  CAS  PubMed  Google Scholar 

  • Diosma G, Romanin DE, Rey-Burusco MF, Londero A, Garrote GL (2014) Yeasts from kefir grains: isolation, identification, and probiotic characterization. World J Microbiol Biotechnol 30:43–53. doi:10.1007/s11274-013-1419-9

    Article  CAS  PubMed  Google Scholar 

  • Douradinha B, Reis VCB, Rogers MB, Torres FAG, Evans JD, Marques ETA (2014) Novel insights in genetic transformation of the probiotic yeast Saccharomyces boulardii. Bioengineered 5:1–9

    Article  Google Scholar 

  • Edwards-Ingram LC, Gent ME, Hoyle DC, Hayes A, Stateva LI, Oliver SG (2004) Comparative genomic hybridization provides new insights into the molecular taxonomy of the Saccharomyces sensu stricto complex. Genome Res 14:1043–1051

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Edwards-Ingram L, Gitsham P, Burton N, Warhurst G, Clarke I, Hoyle D, Oliver SG, Stateva L (2007) Genotypic and physiological characterization of Saccharomyces boulardii, the probiotic strain of Saccharomyces cerevisiae. Appl Env Microbiol 73:2458–2467

    Article  CAS  Google Scholar 

  • Feizizadeh S, Salehi-Abargouei A, Akbari V (2014) Efficacy and safety of Saccharomyces boulardii for acute diarrhea. Pediatrics 134:e176–e191. doi:10.1542/peds.2013-3950

    Article  PubMed  Google Scholar 

  • Ferraretto LF, Shaver RD, Bertics SJ (2012) Effect of dietary supplementation with live-cell yeast at two dosages on lactation performance, ruminal fermentation, and total-tract nutrient digestibility in dairy cows. J Dairy Sci 95:4017–4028. doi:10.3168/jds.2011-5190

    Article  CAS  PubMed  Google Scholar 

  • Fietto JLR, Araújo RS, Valadão FN, Fietto LG, Brandão RL, Neves MJ, Gomes FCO, Nicoli JR, Castro IM (2004) Molecular and physiological comparisons between Saccharomyces cerevisiae and Saccharomyces boulardii. Can J Microbiol 621:615–621

    Article  Google Scholar 

  • Foligné B, Dewulf J, Vandekerckove P, Pignède G, Pot B (2010) Probiotic yeasts: anti-inflammatory potential of various non-pathogenic strains in experimental colitis in mice. World J Gastroenterol 16:2134. doi:10.3748/wjg.v16.i17.2134

    Article  PubMed Central  PubMed  Google Scholar 

  • Gedek BR (1999) Adherence of Escherichia coli serogroup 0 157 and the Salmonella Typhimurium mutant DT 104 to the surface of Saccharomyces boulardii. Mycoses 42:261–264

    Article  CAS  PubMed  Google Scholar 

  • Generoso SV, Viana M, Santos R, Martins FS, Machado JAN, Arantes RME, Nicoli JR, Correia MITD, Cardoso VN (2010) Saccharomyces cerevisiae strain UFMG 905 protects against bacterial translocation, preserves gut barrier integrity and stimulates the immune system in a murine intestinal obstruction model. Arch Microbiol 192:477–484

    Article  CAS  PubMed  Google Scholar 

  • Girardin M, Seidman EG (2011) Indications for the use of probiotics in gastrointestinal diseases. Dig Dis 29:574–587. doi:10.1159/000332980

    Article  PubMed  Google Scholar 

  • Goldstein AL, McCusker JH (1999) Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast 15:1541–1553

    Article  CAS  PubMed  Google Scholar 

  • Gottardi R, Douradinha B (2013) Carbon nanotubes as a novel tool for vaccination against infectious diseases and cancer. J Nanobiotechnol 11:30. doi:10.1186/1477-3155-11-30

    Article  Google Scholar 

  • Gritz L, Davies J, Biogen SA, Acacias R (1983) Plasmid-encoded hygromycin B resistance: the sequence of hygromycin B phosphotransferase gene and its expression in Escherichia coli and Saccharomyces cerevisiae. Gene 25:179–188

    Article  CAS  PubMed  Google Scholar 

  • Hamedi H, Misaghi A, Modarressi MH, Salehi TZ, Khorasanizadeh D, Khalaj V (2013) Generation of a uracil auxotroph strain of the probiotic yeast Saccharomyces boulardii as a host for the recombinant protein production. Avicenna J Med Biotechnol 5:29–34

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hudson LE, Fasken MB, McDermott CD, McBride SM, Kuiper EG, Guiliano DB, Corbett AH, Lamb TJ (2014) Functional heterologous protein expression by genetically engineered probiotic yeast Saccharomyces boulardii. PLoS One 9, e112660

    Article  PubMed Central  PubMed  Google Scholar 

  • Kawai S, Hashimoto W, Murata K (2010) Transformation of Saccharomyces cerevisiae and other fungi: methods and possible underlying mechanism. Bioeng Bugs 1:395–403

    Article  PubMed Central  PubMed  Google Scholar 

  • Khatri I, Akhtar A, Kaur K, Tomar R, Prasad GS, Ramya TNC, Subramanian S (2013) Gleaning evolutionary insights from the genome sequence of a probiotic yeast Saccharomyces boulardii. Gut Pathog 5:30. doi:10.1186/1757-4749-5-30

    Article  PubMed Central  PubMed  Google Scholar 

  • Kourelis A, Kotzamanidis C, Litopoulou-Tzanetaki E, Papaconstantinou J, Tzanetakis N, Yiangou M (2010) Immunostimulatory activity of potential probiotic yeast strains in the dorsal air pouch system and the gut mucosa. J Appl Microbiol 109:260–271. doi:10.1111/j.1365-2672.2009.04651.x

    CAS  PubMed  Google Scholar 

  • Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274

    Article  CAS  PubMed  Google Scholar 

  • Latorre-García L, Adam AC, Polaina J (2008) Overexpression of the glucoamylase-encoding STA1 gene of Saccharomyces cerevisiae var. diastaticus in laboratory and industrial strains of Saccharomyces. World J Microbiol Biotechnol 24:2957–2963

    Article  Google Scholar 

  • Martins FS, Nardi RMD, Arantes RME, Rosa CA, Neves MJ, Nicoli JR (2005) Screening of yeasts as probiotic based on capacities to colonize the gastrointestinal tract and to protect against enteropathogen challenge in mice. J Gen Appl Microbiol 51:83–92

    Article  CAS  PubMed  Google Scholar 

  • Martins FS, Rodrigues ACP, Tiago FCP, Penna FJ, Rosa CA, Arantes RME, Nardi RMD, Neves MJ, Nicoli JR (2007) Saccharomyces cerevisiae strain 905 reduces the translocation of Salmonella enterica serotype Typhimurium and stimulates the immune system in gnotobiotic and conventional mice. J Med Microbiol 56:352–359

    Article  CAS  PubMed  Google Scholar 

  • Martins FS, Dalmasso G, Arantes RME, Doye A, Lemichez E, Lagadec P, Imbert V, Peyron J-F, Rampal P, Nicoli JR, Czerucka D (2010) Interaction of Saccharomyces boulardii with Salmonella enterica serovar Typhimurium protects mice and modifies T84 cell response to the infection. PLoS One 5, e8925

    Article  PubMed Central  PubMed  Google Scholar 

  • Martins FS, Elian SDA, Vieira AT, Tiago FCP, Martins AKS, Silva FCP, Souza ELS, Sousa LP, Araújo HRC, Pimenta PF, Bonjardim CA, Arantes RME, Teixeira MM, Nicoli JR (2011) Oral treatment with Saccharomyces cerevisiae strain UFMG 905 modulates immune responses and interferes with signal pathways involved in the activation of inflammation in a murine model of typhoid fever. Int J Med Microbiol 301:359–364

    Article  PubMed  Google Scholar 

  • Martins FS, Vieira AT, Elian SDA, Arantes RME, Tiago FCP, Sousa LP, Araújo HRC, Pimenta PF, Bonjardim CA, Nicoli JR, Teixeira MM (2013) Inhibition of tissue inflammation and bacterial translocation as one of the protective mechanisms of Saccharomyces boulardii against Salmonella infection in mice. Microbes Infect 15:270–279

    Article  CAS  PubMed  Google Scholar 

  • Mathur S, Singh R (2005) Antibiotic resistance in food lactic acid bacteria—a review. Int J Food Microbiol 105:281–295. doi:10.1016/j.ijfoodmicro.2005.03.008

    Article  CAS  PubMed  Google Scholar 

  • McFarland LV (2010) Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol 16:2202. doi:10.3748/wjg.v16.i18.2202

    Article  PubMed Central  PubMed  Google Scholar 

  • Michael S, Keubler LM, Smoczek A, Meier M, Gunzer F, Pöhlmann C, Krause-Buchholz U, Hedrich H-J, Bleich A (2013) Quantitative phenotyping of inflammatory bowel disease in the IL-10-deficient mouse by use of noninvasive magnetic resonance imaging. Inflamm Bowel Dis 19:185–193

    Article  PubMed  Google Scholar 

  • Mumy KL, Chen X, Kelly CP, McCormick BA (2008) Saccharomyces boulardii interferes with Shigella pathogenesis by postinvasion signaling events. Am J Physiol Gastrointest Liver Physiol 294:G599–G609. doi:10.1152/ajpgi.00391.2007

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • O’Horo JC, Jindai K, Kunzer B, Safdar N (2014) Treatment of recurrent Clostridium difficile infection: a systematic review. Infection 42:43–59. doi:10.1007/s15010-013-0496-x

    Article  PubMed Central  PubMed  Google Scholar 

  • Oliveira AF, Cardoso SA, Almeida FBDR, de Oliveira LL, Pitondo-Silva A, Soares SG, Hanna ES (2012) Oral immunization with attenuated Salmonella vaccine expressing Escherichia coli O157:H7 intimin gamma triggers both systemic and mucosal humoral immunity in mice. Microbiol Immunol 56:513–522

    Article  CAS  PubMed  Google Scholar 

  • Owen JL, Sahay B, Mohamadzadeh M (2013) New generation of oral mucosal vaccines targeting dendritic cells. Curr Opin Chem Biol 17:918–924. doi:10.1016/j.cbpa.2013.06.013

    Article  CAS  PubMed  Google Scholar 

  • Pérez-Sotelo LS, Talavera-Rojas M, Monroy-Salazar HG, Cuarón-Ibargüengoytia JA, Montes R, Jiménez DO, Vázquez-Chagoyán JC (2005) In vitro evaluation of the binding capacity of Saccharomyces cerevisiae Sc47 to adhere to the wall of Salmonella spp. Rev Latinoam Microbiol 47:70–75

    PubMed  Google Scholar 

  • Perricone M, Bevilacqua A, Corbo MR, Sinigaglia M (2014) Technological characterization and probiotic traits of yeasts isolated from Altamura sourdough to select promising microorganisms as functional starter cultures for cereal-based products. Food Microbiol 38:26–35. doi:10.1016/j.fm.2013.08.006

    Article  CAS  PubMed  Google Scholar 

  • Plaza-Diaz J, Gomez-Llorente C, Fontana L, Gil A (2014) Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics. World J Gastroenterol 20:15632–15649. doi:10.3748/wjg.v20.i42.15632

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pohlmann C, Thomas M, Forster S, Brandt M, Hartmann M, Bleich A, Gunzer F (2013) Use of engineered intestinal microorganisms as in situ cytokine delivery system. Bioengineered 4:1–8

    Article  Google Scholar 

  • Pothoulakis C (2009) Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii. Aliment Pharmacol Ther 30:826–833. doi:10.1111/j.1365-2036.2009.04102.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Reis VCB, Nicola AM, de Souza Oliveira Neto O, Batista VDF, de Moraes LMP, Torres FAG (2012) Genetic characterization and construction of an auxotrophic strain of Saccharomyces cerevisiae JP1, a Brazilian industrial yeast strain for bioethanol production. J Ind Microbiol Biotechnol 39:1673–1683

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues ACP, Cara DC, Cunha FQ, Vieira EC, Nicoli JR, Vieira LQ (2000) Saccharomyces boulardii stimulates sIgA production and the phagocytic system of gnotobiotic mice. J Appl Microbiol 89:404–414

    Article  CAS  PubMed  Google Scholar 

  • Romanin D, Serradell M, González Maciel D, Lausada N, Garrote GL, Rumbo M (2010) Down-regulation of intestinal epithelial innate response by probiotic yeasts isolated from kefir. Int J Food Microbiol 140:102–108. doi:10.1016/j.ijfoodmicro.2010.04.014

    Article  CAS  PubMed  Google Scholar 

  • Salyers AA, Gupta A, Wang Y (2004) Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends Microbiol 12:412–416. doi:10.1016/j.tim.2004.07.004

    Article  CAS  PubMed  Google Scholar 

  • Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE (2006) Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis 6:374–382. doi:10.1016/S1473-3099(06)70495-9

    Article  PubMed  Google Scholar 

  • Schneiter R (2004) Genetics, molecular and cell biology of yeast. Université di Fribourg Suisse, Fribourg

    Google Scholar 

  • Sivignon A, de Vallée A, Barnich N, Denizot J, Darcha C, Pignède G, Vandekerckove P, Darfeuille-Michaud A (2015) Saccharomyces cerevisiae CNCM I-3856 prevents colitis induced by AIEC bacteria in the transgenic mouse model mimicking Crohn’s disease. Inflamm Bowel Dis 21:276–286

    Article  PubMed  Google Scholar 

  • Smith IM, Christensen JE, Arneborg N, Jespersen L (2014) Yeast modulation of human dendritic cell cytokine secretion: an in vitro study. PloS Onene 9, e96595. doi:10.1371/journal.pone.0096595

    Article  Google Scholar 

  • Soares RL (2014) Irritable bowel syndrome: a clinical review. World J Gastroenterol 20:12144. doi:10.3748/wjg.v20.i34.12144

    Article  PubMed Central  PubMed  Google Scholar 

  • Sougioultzis S, Simeonidis S, Bhaskar KR, Chen X, Anton PM, Keates S, Pothoulakis C, Kelly CP (2006) Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kappaB-mediated IL-8 gene expression. Biochem Biophys Res Commun 343:69–76. doi:10.1016/j.bbrc.2006.02.080

    Article  CAS  PubMed  Google Scholar 

  • Temmerman R, Pot B, Huys G, Swings J (2003) Identification and antibiotic susceptibility of bacterial isolates from probiotic products. Int J Food Microbiol 81:1–10

    Article  CAS  PubMed  Google Scholar 

  • Tiago FCP, Martins FS, Souza ELS, Pimenta PFP, Araujo HRC, Castro IM, Brandão RL, Nicoli JR (2012) Adhesion to the yeast cell surface as a mechanism for trapping pathogenic bacteria by Saccharomyces probiotics. J Med Microbiol 61:1194–1207

    Article  CAS  PubMed  Google Scholar 

  • Van der Aa Kühle A, Skovgaard K, Jespersen L (2005) In vitro screening of probiotic properties of Saccharomyces cerevisiae var. boulardii and food-borne Saccharomyces cerevisiae strains. Int J Food Microbiol 101:29–39. doi:10.1016/j.ijfoodmicro.2004.10.039

    Article  Google Scholar 

  • Vieira AT, Teixeira MM, Martins FS (2013) The role of probiotics and prebiotics in inducing gut immunity. Front Immunol 4:445. doi:10.3389/fimmu.2013.00445

    Article  PubMed Central  PubMed  Google Scholar 

  • Wang T, Sun H, Zhang J, Liu Q, Wang L, Chen P, Wang F, Li H, Xiao Y, Zhao X (2014) The establishment of Saccharomyces boulardii surface display system using a single expression vector. Fungal Genet Biol 64:1–10

    Article  PubMed  Google Scholar 

  • Whelan K (2007) Enteral-tube-feeding diarrhoea: manipulating the colonic microbiota with probiotics and prebiotics. Proc Nutr Soc 66:299–306. doi:10.1017/S0029665107005551

    Article  PubMed  Google Scholar 

  • Wu X, Vallance BA, Boyer L, Bergstrom KSB, Walker J, Madsen K, O’Kusky JR, Buchan AM, Jacobson K (2008) Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors. Am J Physiol Gastrointest Liver Physiol 294:G295–G306

    Article  CAS  PubMed  Google Scholar 

  • Zanello G, Berri M, Dupont J, Sizaret P-Y, D’Inca R, Salmon H, Meurens F (2011) Saccharomyces cerevisiae modulates immune gene expressions and inhibits ETEC-mediated ERK1/2 and p38 signaling pathways in intestinal epithelial cells. PLoS One 6, e18573. doi:10.1371/journal.pone.0018573

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zanello G, Melo S, Berri M, Inca RD, Auclair E, Salmon H (2013) Effects of dietary yeast strains on immunoglobulin in colostrum and milk of sows. Vet Immunol Immunopathol 152:20–27

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the reviewers for their helpful comments and suggestions. We are grateful to Professor Cláudio A. Masuda, from Universidade Federal do Rio de Janeiro, Brazil, for critically reviewing this manuscript and helpful scientific discussions, and to Stefan Lamers, for English language editing of the manuscript. We thank the funding organisms Fondazione RiMED (Palermo, Italy) and Fundação para o Amparo da Pesquisa do Estado do Rio de Janeiro (FAPERJ, Rio de Janeiro, Brazil).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bruno Douradinha.

Additional information

Mariana L. Palma and Daniel Zamith-Miranda contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Palma, M.L., Zamith-Miranda, D., Martins, F.S. et al. Probiotic Saccharomyces cerevisiae strains as biotherapeutic tools: is there room for improvement?. Appl Microbiol Biotechnol 99, 6563–6570 (2015). https://doi.org/10.1007/s00253-015-6776-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-015-6776-x

Keywords

Navigation