Characteristics and health benefits of the probiotic yeast Saccharomyces boulardii

Abstract

Saccharomyces boulardii is a well-established probiotic yeast with documented clinical benefits for gastrointestinal health. This review highlights the key biotherapeutic mechanisms underlying its protective effects, with particular emphasis on its bioactive metabolites, including specialized enzymes, polyamines, organic acids, and vitamins. These postbiotic factors contribute to epithelial barrier reinforcement, immune modulation, and pathogen exclusion, thereby promoting intestinal homeostasis. In addition, S. boulardii supports microbial equilibrium through colonization resistance and regulation of inflammatory signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells. Clinical evidence demonstrates its efficacy in the prevention and management of antibiotic-associated diarrhea, inflammatory bowel disease, and irritable bowel syndrome. Safety considerations are also addressed, noting its biological distinction from Saccharomyces cerevisiae, particularly its inability to undergo hyphal transformation. Owing to its resilience against gastric acidity, bile salts, and concomitant antibiotic therapy, S. boulardii represents a valuable adjunct in contemporary gastrointestinal therapeutics and a promising platform for functional and translational applications.

Keywords

Saccharomyces boulardii / Probiotic / Yeast / Bioactive / Metabolites / Enzymes / Microbiome / Functional foods

References

[1] Dahiya D, Terpou A, Nigam PS. Strategic Restoration of Sustainability in Gut Microbiome Diversity Through Synbiotic Food, Functional Beverages or Commercial Probiotic Formulations: Achieving Sustainable Development Goals 03, 09 and 12. SCI Sustainability. 2025;1(1):e70004. doi: 10.1002/sst2.70004

[2] Terpou A, Dahiya D, Nigam PS. Evolving Dynamics of Fermented Food Microbiota and the Gut Microenvironment: Strategic Pathways to Enhance Human Health. Foods. 2025; 14(13):2361. doi: 10.3390/foods14132361

[3] Pais P, Almeida V, Yılmaz M, Teixeira MC. Saccharomyces boulardii: what makes it tick as successful probiotic? J Fungi. 2020; 6(2):78. doi: 10.3390/jof6020078

[4] Tomičić Z, Šarić L, Tomičić R. Novel insights in the application of probiotic yeast Saccharomyces boulardii in dairy products and health promotion. Foods. 2024; 13(18):2866. doi: 10.3390/foods13182866

[5] Dahiya D, Nigam PS. Nutraceuticals prepared with specific strains of probiotics for supplementing gut microbiota in hosts allergic to certain foods or their additives. Nutrients. 2023; 15(13):2979. doi: 10.3390/nu15132979

[6] Huang Z, Brot L, Fatouh R, et al. Saccharomyces boulardii CNCM I-745 mitigates antibiotic-induced gut microbiome functional alterations independently of the host. Gut Microbes. 2025; 17(1):2575924. doi: 10.1080/19490976.2025.2575924

[7] Özlük G, Krausová G. Gastric survival of lactic acid bacteria in probiotic-labelled products from the Turkish market: An in vitro study. Czech J Food Sci. 2025. doi: 10.17221/36/2025-CJFS

[8] Kelesidis T, Pothoulakis C. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Ther Adv Gastroenterol. 2012; 5(2):111-125. doi: 10.1177/1756283X11428502

[9] Pal BB, Bandagi RV, Pebbili KK, et al. Effectiveness of Saccharomyces boulardii CNCM I-745 in adult Indian patients with diarrhoea: A real-world, multicentre, retrospective, comparative study. Drugs Real World Outcomes. 2024; 11(2):309-316. doi: 10.1007/s40801-024-00424-3

[10] Dahiya D, Nigam PS. Biotherapy Using Probiotics as Therapeutic Agents to Restore the Gut Microbiota to Relieve Gastrointestinal Tract Inflammation, IBD, IBS and Prevent Induction of Cancer. Int J Mol Sci. 2023; 24:5748. doi: 10.3390/ijms24065748

[11] Khatri I, Tomar R, Ganesan K, Prasad G, Subramanian S. Complete genome sequence and comparative genomics of the probiotic yeast Saccharomyces boulardii. Sci Rep. 2017; 7(1):371. doi: 10.1038/s41598-017-00414-2

[12] Gopalan S, Ganapathy S, Mitra M, et al. Unique properties of yeast probiotic Saccharomyces boulardii CNCM I-745: A narrative review. Cureus. 2023; 15(10):e46314. doi: 10.7759/cureus.46314

[13] Kaźmierczak-Siedlecka K, Ruszkowski J, Fic M, Folwarski M, Makarewicz W. Saccharomyces boulardii CNCM I-745: a non-bacterial microorganism used as probiotic agent in supporting treatment of selected diseases. Curr Microbiol. 2020; 77(9):1987. doi: 10.1007/s00284-020-02053-9

[14] Lacotte P-A, Simons A, Bouttier S, Malet-Villemagne J, Nicolas V, Janoir C. Inhibition of in vitro Clostridioides difficile biofilm formation by the probiotic yeast Saccharomyces boulardii CNCM I-745 through modification of the extracellular matrix composition. Microorganisms. 2022; 10(6):1082. doi: 10.3390/microorganisms10061082

[15] Tukaram KS, Sopanrao SR, Kacharu LO. Unveiling The Therapeutic Potential of Probiotics: A Review. J Future Foods. 2025. doi: 10.1016/j.jfutfo.2025.09.011

[16] Hijová E. Postbiotics as metabolites and their biotherapeutic potential. Int J Mol Sci. 2024; 25(10):5441. doi: 10.3390/ijms25105441

[17] Edkaidek H, Dahiya D, Nigam PS. Prospects of Bioactive Compounds in Designing Functional Foods: Challenges and Solutions. Foods. 2026; 15(8):1291. doi: 10.3390/foods15081291

[18] Kurtzman C, Fell JW, Boekhout T. The Yeasts: A Taxonomic Study . Elsevier; 2011.

[19] Shi S, Chen Y, Nielsen J. Metabolic engineering of yeast. Annu Rev Biophys. 2025; 54. doi: 10.1146/annurev-biophys-070924-103134

[20] Pais P, Oliveira J, Almeida V, Yilmaz M, Monteiro PT, Teixeira MC. Transcriptome-wide differences between Saccharomyces cerevisiae and Saccharomyces cerevisiae var. boulardii: Clues on host survival and probiotic activity based on promoter sequence variability. Genomics. 2021; 113(2):530-539. doi: 10.1016/j.ygeno.2020.11.034

[21] Wang Z, Xu W, Gao Y, et al. Engineering Saccharomyces cerevisiae for improved biofilm formation and ethanol production in continuous fermentation. Biotechnol Biofuels Bioprod. 2023; 16(1):119. doi: 10.1186/s13068-023-02356-6

[22] Liu J-J, Zhang G-C, Kong II, et al. A mutation in PGM2 causing inefficient galactose metabolism in the probiotic yeast Saccharomyces boulardii. Appl Environ Microbiol. 2018; 84(10):e02858-17. doi: 10.1128/AEM.02858-17

[23] Filipe Rosa L, Gonda S, Roese N, Bischoff SC. Saccharomyces boulardii CNCM I-745 Supernatant Improves Markers of Gut Barrier Function and Inflammatory Response in Small Intestinal Organoids. Pharmaceuticals. 2025; 18(8):1167. doi:10.3390/ph18081167

[24] Dahiya D, Nigam PS. Nutraceutical Combinational Therapy for Diarrhoea Control with Probiotic Beverages from Fermented Fruits, Vegetables and Cereals to Regain Lost Hydration, Nutrition and Gut Microbiota. Microorganisms. 2023; 11:2190. doi: 10.3390/microorganisms11092190

[25] Li B, Zhang H, Shi L, et al. Saccharomyces boulardii alleviates DSS-induced intestinal barrier dysfunction and inflammation in humanized mice. Food Funct. 2022; 13(1):102-112. doi: 10.1039/D1FO02752B

[26] Buts J-P, De Keyser N, Stilmant C, Sokal E, Marandi S. Saccharomyces boulardii enhances N-terminal peptide hydrolysis in suckling rat small intestine by endoluminal release of a zinc-binding metalloprotease. Pediatr Res. 2002; 51(4):528-534. doi: 10.1203/00006450-200204000-00021

[27] Pothoulakis C. Anti-inflammatory mechanisms of action of Saccharomyces boulardii. Aliment Pharmacol Ther. 2009; 30(8):826-833. doi: 10.1111/j.1365-2036.2009.04102.x

[28] Czerucka D, Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. World J Gastroenterol. 2019; 25(18):2188. doi: 10.3748/wjg.v25.i18.2188

[29] Chen X, Kokkotou EG, Mustafa N, et al. Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against Clostridium difficile toxin A-induced enteritis. J Biol Chem. 2006; 281(34):24449-24454. doi: 10.1074/jbc.M605200200

[30] Moré MI, Vandenplas Y. Saccharomyces boulardii CNCM I-745 improves intestinal enzyme function: a trophic effects review. Clin Med Insights Gastroenterol. 2018; 11:1179552217752679. doi: 10.1177/1179552217752679

[31] Castagliuolo I, Lamont JT, Nikulasson ST, Pothoulakis C. Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun. 1996; 64(12):5225-5232. doi: 10.1128/iai.64.12.5225-5232.1996

[32] Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun. 1999; 67(1):302-307. doi: 10.1128/IAI.67.1.302-307.1999

[33] Pereira KN, de Oliveira ACD, de Souza HF, et al. Application of Saccharomyces cerevisiae var. boulardii for Biological Detoxification of Chemical Contaminants in Foods: A Comprehensive Review. Foods. 2025; 14(24):4260. doi: 10.3390/foods14244260

[34] Buts J-P, Dekeyser N, Stilmant C, Delem E, Smets F, Sokal E. Saccharomyces boulardii produces in rat small intestine a novel protein phosphatase that inhibits Escherichia coli endotoxin by dephosphorylation. Pediatr Res. 2006; 60(1):24-29. doi: 10.1203/01.pdr.0000220322.31940.29

[35] Buts J-p, Keyser ND, Raedemaeker LD. Saccharomyces boulardii enhances rat intestinal enzyme expression by endoluminal release of polyamines. Pediatr Res. 1994; 36(4):522-527. doi: 10.1203/01.pdr.0000220322.31940.29

[36] Dahiya D, Nigam PS. Therapeutic and Dietary Support for Gastrointestinal Tract Using Kefir as a Nutraceutical Beverage: Dairy-Milk-Based or Plant-Sourced Kefir Probiotic Products for Vegan and Lactose-Intolerant Populations. Fermentation. 2023; 9:388. doi: 10.3390/fermentation9040388

[37] Remenova T, Morand O, Amato D, Chadha-Boreham H, Tsurutani S, Marquardt T. A double-blind, randomized, placebo-controlled trial studying the effects of Saccharomyces boulardii on the gastrointestinal tolerability, safety, and pharmacokinetics of miglustat. Orphanet J Rare Dis. 2015; 10(1):81. doi: 10.1186/s13023-015-0297-7

[38] Joudaki H, Aria N, Moravej R, Yazdi MR, Emami-Karvani Z, Hamblin MR. Microbial phytases: properties and applications in the food industry. Curr Microbiol. 2023; 80(12):374. doi: 10.1007/s00284-023-03471-1

[39] Buts J-P, Stilmant C, Bernasconi P, Neirinck C, De Keyser N. Characterization of α,α-trehalase released in the intestinal lumen by the probiotic Saccharomyces boulardii. Scand J Gastroenterol. 2008; 43(12):1489-1496. doi: 10.1080/00365520802308862

[40] Tang S, Li J, Li Y, et al. Effects of Saccharomyces boulardii on microbiota composition and metabolite levels in the small intestine of constipated mice. BMC Microbiol. 2024; 24(1):493. doi: 10.1186/s12866-024-03647-0

[41] Goktas H, Agan C, Bekiroglu H, Bozkurt F, Sagdic O. Production of exopolysaccharide from probiotic Saccharomyces cerevisiae var. boulardii S11 and determination of its structural, rheological, antioxidant and prebiotic properties. Food Sci Biotechnol. 2025:1-11. doi: 10.1007/s10068-025-02018-3

[42] Vilanculos SL, Svanberg U, Andlid T. Phytate degradation in composite wheat/cassava/sorghum bread: Effects of phytase-secreting yeasts and addition of yeast extracts. Food Sci Nutr. 2024; 12(1):216-226. doi: 10.1002/fsn3.3754

[43] Wang D, Wang L, Liu S, et al. Proteomic and Functional Analyses Reveal the Stress Tolerance Network in Saccharomyces boulardii during Gastrointestinal Challenge. J Proteome Res. 2025; 25(1):244-252. doi: 10.1021/acs.jproteome.5c00470

[44] Zhang C, Zhen Y, Weng Y, et al. Research progress on the microbial metabolism and transport of polyamines and their roles in animal gut homeostasis. J Anim Sci Biotechnol. 2025; 16(1):57. doi: 10.1186/s40104-025-01193-x

[45] Igarashi K, Kashiwagi K. Modulation of cellular function by polyamines. Int J Biochem Cell Biol. 2010; 42(1):39-51. doi: 10.1016/j.biocel.2009.07.009

[46] Miller-Fleming L, Olin-Sandoval V, Campbell K, Ralser M. Remaining mysteries of molecular biology: the role of polyamines in the cell. J Mol Biol. 2015; 427(21):3389-3406. doi: 10.1016/j.jmb.2015.06.020

[47] Czerucka D, Piche T, Rampal P. Yeast as probiotics - Saccharomyces boulardii. Aliment Pharmacol Ther. 2007; 26(6):767-778. doi: 10.1111/j.1365-2036.2007.03442.x

[48] Fu J, Liu J, Wen X, et al. Unique probiotic properties and bioactive metabolites of Saccharomyces boulardii. Probiotics Antimicrob Proteins. 2023; 15(4):967-982. doi: 10.1007/s12602-022-09953-1

[49] Albenberg L, Esipova TV, Judge CP, et al. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology. 2014; 147(5):1055-1063.e8. doi: 10.1053/j.gastro.2014.07.020

[50] de Carvalho BT, Subotić A, Vandecruys P, Deleu S, Vermeire S, Thevelein JM. Enhancing probiotic impact: engineering Saccharomyces boulardii for optimal acetic acid production and gastric passage tolerance. Appl Environ Microbiol. 2024; 90(6):e00325-24. doi: 10.1128/aem.00325-24

[51] Dahiya D, Nigam PS. Antibiotic-Therapy-Induced Gut Dysbiosis Affecting Gut Microbiota-Brain Axis and Cognition: Restoration by Intake of Probiotics and Synbiotics. Int J Mol Sci. 2023; 24:3074. doi: 10.3390/ijms24043074

[52] Chandrasekar Rajendran S, Chamlagain B, Kariluoto S, Piironen V, Saris PE. Biofortification of riboflavin and folate in idli batter, based on fermented cereal and pulse, by Lactococcus lactis N8 and Saccharomyces boulardii SAA655. J Appl Microbiol. 2017; 122(6):1663-1671. doi: 10.1111/jam.13453

[53] Polat Kaya H, Kaya B, Tuncel NB, et al. Fermentation of Sainfoin Seed Flour with Saccharomyces boulardii: Effects on Total Dietary Fiber, Anti-Nutrients, Antimicrobial Activity, and Bioaccessibility of Bioactive Compounds. Microorganisms. 2025; 13(6):1421. doi: 10.3390/microorganisms13061421

[54] Dahiya D, Nigam PS. Inclusion of Dietary-Fibers in Nutrition Provides Prebiotic Substrates to Probiotics for the Synthesis of Beneficial Metabolites SCFA to Sustain Gut Health Minimizing Risk of IBS, IBD, CRC. Recent Prog Nutr. 2023;3(3):017. doi: 10.21926/rpn.2303017

[55] Lyon P, Strippoli V, Fang B, Cimmino L. B vitamins and one-carbon metabolism: implications in human health and disease. Nutrients. 2020; 12(9):2867. doi: 10.3390/nu12092867

[56] Dahiya D, Nigam PS. Use of Characterized Microorganisms in Fermentation of Non-Dairy-Based Substrates to Produce Probiotic Food for Gut-Health and Nutrition. Fermentation. 2023; 9:1-12. doi: 10.3390/fermentation9010001

[57] Dahiya D, Nigam PS. Nutrition and Health through the Use of Probiotic Strains in Fermentation to Produce Non-Dairy Functional Beverage Products Supporting Gut Microbiota. Foods. 2022; 11(18):2760. doi: 10.3390/foods11182760

[58] Dahiya D, Nigam PS. Probiotics, Prebiotics, Synbiotics, and Fermented Foods as potential biotics in Nutrition Improving Health via Microbiome-Gut-Brain Axis. Fermentation. 2022; 8:303. doi: 10.3390/fermentation8070303

[59] Dahiya D, Nigam PS. The gut microbiota influenced by the intake of probiotics and functional foods with prebiotics can sustain wellness and alleviate certain ailments like gut-inflammation and colon-cancer. Microorganisms. 2022; 10(3):665. doi: 10.3390/microorganisms10030665

[60] McFarland L. Common organisms and probiotics: Saccharomyces boulardii. In: The Microbiota in Gastrointestinal Pathophysiology . Elsevier; 2017:145-164. doi: 10.1016/B978-0-12-804024-9.00018-5

[61] Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Mechanisms of action of probiotics. Adv Nutr. 2019; 10:S49-S66. doi: 10.1093/advances/nmy063

[62] Dahiya D, Nigam PS. Clinical Potential of Microbial Strains, Used in Fermentation for Probiotic Food, Beverages and in Synbiotic Supplements, as Psychobiotics for Cognitive Treatment through Gut-Brain Signaling. Microorganisms. 2022; 10(9):1687. doi: 10.3390/microorganisms10091687

[63] Xu X, Wu J, Jin Y, Huang K, Zhang Y, Liang Z. Both Saccharomyces boulardii and its postbiotics alleviate dextran sulfate sodium-induced colitis in mice, association with modulating inflammation and intestinal microbiota. Nutrients. 2023; 15(6):1484. doi: 10.3390/nu15061484

[64] McFarland LV. Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review. BMJ Open. 2014; 4(8):e005047. doi: 10.1136/bmjopen-2014-005047

[65] Ceapa C, Wopereis H, Rezaïki L, Kleerebezem M, Knol J, Oozeer R. Influence of fermented milk products, prebiotics and probiotics on microbiota composition and health. Best Pract Res Clin Gastroenterol. 2013; 27(1):139-155. doi: 10.1016/j.bpg.2013.04.004

[66] Dahan S, Dalmasso G, Imbert V, Peyron J-F, Rampal P, Czerucka D. Saccharomyces boulardii interferes with enterohemorrhagic Escherichia coli-induced signaling pathways in T84 cells. Infect Immun. 2003; 71(2):766-773. doi: 10.1128/IAI.71.2.766-773.2003

[67] Elkoumi O, Elkoumi A, Elbairy MK, et al. P-157. Efficacy and Safety of Helicobacter pylori Triple Therapy With and Without Saccharomyces boulardii Supplementation: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. Oxford University Press US. 2026:ofaf695.381.

[68] Ouwehand AC, Salminen S, Isolauri E. Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek. 2002; 82(1):279-289. doi: 10.1023/A:1020620607611

[69] Edwards-Ingram LC, Gent ME, Hoyle DC, Hayes A, Stateva LI, Oliver SG. Comparative genomic hybridization provides new insights into the molecular taxonomy of the Saccharomyces sensu stricto complex. Genome Res. 2004; 14(6):1043-1051. doi: 10.1101/gr.2114704

[70] Tiago F, Martins F, Souza E, et al. Adhesion to the yeast cell surface as a mechanism for trapping pathogenic bacteria by Saccharomyces probiotics. J Med Microbiol. 2012; 61(9):1194-1207. doi: 10.1099/jmm.0.042283-0

[71] Larabi AB, Masson HL, Bäumler AJ. Bile acids as modulators of gut microbiota composition and function. Gut Microbes. 2023; 15(1):2172671. doi: 10.1080/19490976.2023.2172671

[72] Klein SM, Elmer GW, McFarland LV, Surawicz CM, Levy RH. Recovery and elimination of the biotherapeutic agent, Saccharomyces boulardii, in healthy human volunteers. Pharm Res. 1993; 10(11):1615-1619. doi: 10.1023/A:1018924820333

[73] Gao H, Li Y, Xu J, et al. Saccharomyces boulardii protects against murine experimental colitis by reshaping the gut microbiome and its metabolic profile. Front Microbiol. 2023; 14:1204122. doi: 10.3389/fmicb.2023.1204122

[74] Vijayaram S, Vivekanandan K, Kandasamy S, et al. Probiotics: A multifaceted approach to health promotion- from disease prevention to food enrichment and delivery systems. AIMS Microbiol. 2025; 11(3):602. doi: 10.3934/microbiol.2025026

[75] Bahuguna N, Venugopal D, Rai N. Biotherapeutic potential of probiotic yeast Saccharomyces boulardii against Candida albicans biofilm. Indian J Microbiol. 2025; 65(3):1534-1545. doi: 10.1007/s12088-024-01350-2

[76] Gao H, Li Y, Sun J, et al. Saccharomyces boulardii Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Regulating NF-κB and Nrf2 Signaling Pathways. Oxid Med Cell Longev. 2021; 2021:1622375. doi: 10.1155/2021/1622375

[77] Pontier-Bres R, Munro P, Boyer L, et al. Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract. PLoS ONE. 2014; 9(8):e103069. doi: 10.1371/journal.pone.0103069

[78] Rodrigues A, Cara DC, Fretez S, et al. Saccharomyces boulardii stimulates sIgA production and the phagocytic system of gnotobiotic mice. J Appl Microbiol. 2000; 89(3):404-414. doi: 10.1046/j.1365-2672.2000.01128.x

[79] Di Martino L, Osme A, Ghannoum M, Cominelli F. A novel probiotic combination ameliorates Crohn’s disease-like ileitis by increasing short-chain fatty acid production and modulating essential adaptive immune pathways. Inflamm Bowel Dis. 2023; 29(7):1105-1117. doi: 10.1093/ibd/izac284

[80] McCole DF. Brewing a Cure: Engineering Yeast to Reduce Inflammation-Driven Tumors. Dig Dis Sci. 2025:1-3. doi: 10.1007/s10620-025-09194-6

[81] Dos Santos JFdM, Mello IS, da Cruz ILS, Soares MA. Non-Saccharomyces yeasts contribute to longevity, mitigated protein toxicity, and protection against abiotic stress in Caenorhabditis elegans. Arch Microbiol. 2026; 208(3):128. doi: 10.1007/s00203-025-04665-w

[82] McFarland LV. Efficacy of single-strain probiotics versus multi-strain mixtures: systematic review of strain and disease specificity. Dig Dis Sci. 2021; 66(3):694-704. doi: 10.1007/s10620-020-06244-z

[83] Jahn H-U, Ullrich R, Schneider T, et al. Immunological and trophical effects of Saccharomyces boulardii on the small intestine in healthy human volunteers. Digestion. 1996; 57(2):95-104. doi: 10.1159/000201320

[84] Offei B, Vandecruys P, De Graeve S, Foulquié-Moreno MR, Thevelein JM. Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. boulardii. Genome Res. 2019; 29(9):1478-1494. doi: 10.1101/gr.243147.118

[85] Fukuda S, Toh H, Hase K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011; 469(7331):543-547. doi: 10.1038/nature09646

[86] Buts J-P, Keyser ND. Transduction pathways regulating the trophic effects of Saccharomyces boulardii in rat intestinal mucosa. Scand J Gastroenterol. 2010; 45(2):175-185. doi: 10.3109/00365520903453141

[87] Buts J, Dekeyser N. Raf: a key regulatory kinase for transduction of mitogenic and metabolic signals of the probiotic Saccharomyces boulardii. Clin Res Hepatol Gastroenterol. 2011; 35(8-9):596-597. doi: 10.1016/j.clinre.2011.04.010

[88] McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010; 16(18):2202. doi: 10.3748/wjg.v16.i18.2202

[89] Kollaritsch H, Holst H, Grobara P, Wiedermann G. Prevention of traveler’s diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study. Fortschr Med. 1993; 111(9):152-156.

[90] Szajewska H, Horvath A, Piwowarczyk A. Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment. Aliment Pharmacol Ther. 2010; 32(9):1069-1079. doi: 10.1111/j.1365-2036.2010.04457.x

[91] McFarland LV. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA. 1994; 271:1913-1918. doi: 10.1001/jama.1994.03510480037031

[92] Dinleyici EC, Kara A, Ozen M, Vandenplas Y. Saccharomyces boulardii CNCM I-745 in different clinical conditions. Expert Opin Biol Ther. 2014; 14(11):1593-1609. doi: 10.1517/14712598.2014.937419

[93] Surawicz CM, McFarland LV, Greenberg RN, et al. The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis. 2000; 31(4):1012-1017. doi: 10.1086/318130

[94] Cayzeele-Decherf A, Pélerin F, Leuillet S, et al. Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis. World J Gastroenterol. 2017; 23(2):336. doi: 10.3748/wjg.v23.i2.336

[95] Everard A, Matamoros S, Geurts L, Delzenne NM, Cani PD. Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. mBio. 2014; 5(3):e01011-14. doi: 10.1128/mBio.01011-14

[96] Chondrou T, Adamidi N, Lygouras D, Hirota SA, Androutsos O, Svolos V. Dietary Phytic Acid, Dephytinization, and Phytase Supplementation Alter Trace Element Bioavailability-A Narrative Review of Human Interventions. Nutrients. 2024; 16(23):4069. doi: 10.3390/nu16234069

[97] Richards JD, Cori H, Rahn M, et al. Micronutrient bioavailability: Concepts, influencing factors, and strategies for improvement. Front Nutr . 2025; 12:1646750. doi: 10.3389/fnut.2025.1646750

[98] Sandberg A-S. The effect of food processing on phytate hydrolysis and availability of iron and zinc. In: Nutritional and Toxicological Consequences of Food Processing . 1991:499-508. doi: 10.1007/978-1-4899-2626-5_33

[99] Czech A, Samolińska W, Tomaszewska E, Muszyński S, Grela ER. Effect of microbial phytase on ileal digestibility of minerals, plasma and urine metabolites, and bone mineral concentrations in growing-finishing pigs. Animals. 2022; 12(10):1294. doi: 10.3390/ani12101294

[100] Shikh E, Makhova A, Dorogun O, Elizarova E. The role of phytates in human nutrition. Vopr Pitan. 2023; 92(4):20-28. doi: 10.33029/0042-8833-2023-92-4-20-28

[101] Sanchis P, López-González Á-A, Costa-Bauzá A, et al. Understanding the protective effect of phytate in bone decalcification related-diseases. Nutrients. 2021; 13(8):2859. doi: 10.3390/nu13082859

[102] Saverino A, Shamsuddin AM, Vucenik I. IP6: From Seeds to Science-A Natural Compound’s Path to Clinical Promise. Biomolecules. 2025; 15(12):1652. doi: 10.3390/biom15121652

[103] Vucenik I, Shamsuddin AM. Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic. J Nutr. 2003; 133(11):3778S-3784S. doi: 10.1093/jn/133.11.3778S

[104] Vucenik I, Shamsuddin AM. Protection against cancer by dietary IP6 and inositol. Nutr Cancer . 2006; 55(2):109-125. doi: 10.1207/s15327914nc5502_1

[105] Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022; 80(4):931-949. doi: 10.1093/nutrit/nuab057

[106] Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr. 2012; 3(1):21-38. doi: 10.3945/an.111.000992

[107] Otsu Y, Ae R, Kuwabara M. Folate and cardiovascular disease. Hypertens Res. 2023; 46(7):1816-1818. doi: 10.1038/s41440-023-01307-w

[108] Bjørke-Monsen A-L, Lysne V. Vitamin B12-a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res. 2023; 67:10257. doi: 10.29219/fnr.v67.10257

[109] Wang X, Yu M, Ye J, et al. Research advances on encapsulation of probiotics with nanomaterials and their repair mechanisms on intestinal barriers. Food Sci Hum Wellness. 2024; 13(6):3095-3109. doi: 10.26599/FSHW.2022.9250246

[110] Moslehi-Jenabian S, Pedersen LL, Jespersen L. Beneficial effects of probiotic and food borne yeasts on human health. Nutrients. 2010; 2(4):449-473. doi: 10.3390/nu2040449

[111] Sun Y, Rajput IR, Arain MA, Li Y, Baloch DM. Oral administration of Saccharomyces boulardii alters duodenal morphology, enzymatic activity and cytokine production response in broiler chickens. Anim Sci J. 2017; 88(8):1204-1211. doi: 10.1111/asj.12757

[112] Terciolo C, Dobric A, Ouaissi M, et al. Saccharomyces boulardii CNCM I-745 restores intestinal barrier integrity by regulation of E-cadherin recycling. J Crohns Colitis. 2017; 11(8):999-1010. doi: 10.1093/ecco-jcc/jjx030

[113] Cario E. Barrier-protective function of intestinal epithelial Toll-like receptor 2. Mucosal Immunol. 2008; 1:S62-S66. doi: 10.1038/mi.2008.47

[114] Oppong GO, Rapsinski GJ, Newman TN, Nishimori JH, Biesecker SG, Tükel Ç. Epithelial cells augment barrier function via activation of the Toll-like receptor 2/phosphatidylinositol 3-kinase pathway upon recognition of Salmonella enterica serovar Typhimurium curli fibrils in the gut. Infect Immun. 2013; 81(2):478-486. doi: 10.1128/iai.00453-12

[115] Szajewska H, Guarino A, Hojsak I, et al. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014; 58(4):531-539. doi: 10.1097/MPG.0000000000000320

[116] Buts J-P, Bernasconi P, Van Craynest M-P, Maldague P, De Meyer R. Response of human and rat small intestinal mucosa to oral administration of Saccharomyces boulardii. Pediatr Res. 1986; 20(2):192-196. doi: 10.1203/00006450-198602000-00020

[117] Dalmasso G, Cottrez F, Imbert V, et al. Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Gastroenterology. 2006; 131(6):1812-1825. doi: 10.1053/j.gastro.2006.10.001

[118] Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol. 2021; 12:578386. doi: 10.3389/fimmu.2021.578386

[119] Kline KA, Fälker S, Dahlberg S, Normark S, Henriques-Normark B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe. 2009; 5(6):580-592. doi: 10.1016/j.chom.2009.05.011

[120] Thomas S, Przesdzing I, Metzke D, Schmitz J, Radbruch A, Baumgart D. Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation. Clin Exp Immunol. 2009; 156(1):78-87. doi: 10.1111/j.1365-2249.2009.03878.x

[121] Bohn JA, BeMiller JN. (1→3)-β-d-Glucans as biological response modifiers: a review of structure-functional activity relationships. Carbohydr Polym. 1995; 28(1):3-14. doi: 10.1016/0144-8617(95)00076-3

[122] Brown GD, Herre J, Williams DL, Willment JA, Marshall AS, Gordon S. Dectin-1 mediates the biological effects of β-glucans. J Exp Med. 2003; 197(9):1119-1124. doi: 10.1084/jem.20021890

[123] Rice PJ, Kelley JL, Kogan G, et al. Human monocyte scavenger receptors are pattern recognition receptors for (1→3)-β-D-glucans. J Leukoc Biol. 2002; 72(1):140-146. doi: 10.1189/jlb.72.1.140

[124] Yang Z, Wu Y, Liu X, Zhang M, Peng J, Wei H. S. boulardii early intervention maintains gut microbiome structure and promotes gut mucosal barrier function in early-weaned rats. Nutrients. 2022; 14(17):3485. doi: 10.3390/nu14173485

[125] Reale A, Mannina L, Tremonte P, et al. Phytate degradation by lactic acid bacteria and yeasts during the wholemeal dough fermentation: a 31P NMR study. J Agric Food Chem. 2004; 52(20):6300-6305. doi: 10.1021/jf049551p

[126] Sarwar A, Aziz T, Al-Dalali S, et al. Physicochemical and microbiological properties of synbiotic yogurt made with probiotic yeast Saccharomyces boulardii in combination with inulin. Foods. 2019; 8(10):468. doi: 10.3390/foods8100468

[127] Sarwar A, Al-Dalali S, Aziz T, et al. Effect of chilled storage on antioxidant capacities and volatile flavors of synbiotic yogurt made with probiotic yeast Saccharomyces boulardii CNCM I-745 in combination with inulin. J Fungi. 2022; 8(7):713. doi: 10.3390/jof8070713

[128] Türk M, Sandberg A-S, Carlsson N-G, Andlid T. Inositol hexaphosphate hydrolysis by Baker’s yeast. Capacity, kinetics, and degradation products. J Agric Food Chem. 2000; 48(1):100-104. doi: 10.1021/jf9901892

[129] Lopez HW, Duclos V, Coudray C, et al. Making bread with sourdough improves mineral bioavailability from reconstituted whole wheat flour in rats. Nutrition. 2003; 19(6):524-530. doi: 10.1016/s0899-9007(02)01079-1

[130] Chaoui A, Faid M, Belhcen R. Effect of natural starters for Sourdough bread in Morocco on phytate biodegradation. East Mediterr Health J. 2003; 9(1-2):141-147. doi: 10.26719/2003.9.1-2.141

[131] Haefner S, Knietsch A, Scholten E, Braun J, Lohscheidt M, Zelder O. Biotechnological production and applications of phytases. Appl Microbiol Biotechnol. 2005; 68(5):588-597. doi: 10.1007/s00253-005-0005-y

[132] Choudhury N, Meghwal M, Das K. Microencapsulation: An overview on concepts, methods, properties and applications in foods. Food Front. 2021; 2(4):426-442. doi: 10.1002/fft2.94

[133] Vohra A, Satyanarayana T. Phytases: microbial sources, production, purification, and potential biotechnological applications. Crit Rev Biotechnol. 2003; 23(1):29-60. doi: 10.1080/713609297

[134] Vucenik I. Anticancer properties of inositol hexaphosphate and inositol: An overview. J Nutr Sci Vitaminol. 2019; 65(Supplement):S18-S22. doi: 10.3177/jnsv.65.S18

[135] Kariluoto S, Aittamaa M, Korhola M, Salovaara H, Vahteristo L, Piironen V. Effects of yeasts and bacteria on the levels of folates in rye sourdoughs. Int J Food Microbiol. 2006; 106(2):137-143. doi: 10.1016/j.ijfoodmicro.2005.06.013

[136] Patring JD, Hjortmo SB, Jastrebova JA, Svensson UK, Andlid TA, Jägerstad IM. Characterization and quantification of folates produced by yeast strains isolated from kefir granules. Eur Food Res Technol. 2006; 223(5):633-637. doi: 10.1007/s00217-005-0245-1

[137] Zubillaga M, Weill R, Postaire E, Goldman C, Caro R, Boccio J. Effect of probiotics and functional foods and their use in different diseases. Nutr Res. 2001; 21(3):569-579. doi: 10.1016/S0271-5317(01)00281-0

[138] Jägerstad M, Piironen V, Walker C, et al. Increasing natural food folates through bioprocessing and biotechnology. Trends Food Sci Technol. 2005; 16(6-7):298-306. doi: 10.1016/j.tifs.2005.03.005

[139] Corrêa NB, Penna FJ, Lima FM, Nicoli JR, Filho LA. Treatment of acute diarrhea with Saccharomyces boulardii in infants. J Pediatr Gastroenterol Nutr. 2011; 53(5):497-501. doi: 10.1097/MPG.0b013e31822b7ab0

[140] McFarland LV, Li T. Efficacy and safety of Saccharomyces boulardii CNCM I-745 for the treatment of pediatric acute diarrhea in China: a systematic review and meta-analysis. Front Cell Infect Microbiol. 2025; 15:1587792. doi: 10.3389/fcimb.2025.1587792

[141] Szajewska H, Mrukowicz J. Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2005; 22(5):365-372. doi: 10.1111/j.1365-2036.2005.02624.x

[142] Karpa KD. Probiotics for Clostridium difficile diarrhea: putting it into perspective. Ann Pharmacother. 2007; 41(7-8):1284-1287. doi: 10.1345/aph.1K228

[143] Lherm T, Monet C, Nougière B, et al. Seven cases of fungemia with Saccharomyces boulardii in critically ill patients. Intensive Care Med. 2002; 28(6):797-801. doi: 10.1007/s00134-002-1267-9

[144] Thygesen JB, Glerup H, Tarp B. Saccharomyces boulardii fungemia caused by treatment with a probioticum. BMJ Case Rep. 2012; 2012:bcr0620114412. doi: 10.1136/bcr.06.2011.4412

[145] Appel-da-Silva MC, Narvaez GA, Perez LR, Drehmer L, Lewgoy J. Saccharomyces cerevisiae var. boulardii fungemia following probiotic treatment. Med Mycol Case Rep. 2017; 18:15-17. doi: 10.1016/j.mmcr.2017.07.007

[146] Cassone M, Serra P, Mondello F, et al. Outbreak of Saccharomyces cerevisiae subtype boulardii fungemia in patients neighboring those treated with a probiotic preparation of the organism. J Clin Microbiol. 2003; 41(11):5340-5343. doi: 10.1128/jcm.41.11.5340-5343.2003

[147] Poncelet A, Ruelle L, Konopnicki D, Deyi VM, Dauby N. Saccharomyces cerevisiae fungemia: Risk factors, outcome and links with S. boulardii-containing probiotic administration. Infect Dis Now. 2021; 51(3):293-295. doi: 10.1016/j.idnow.2020.12.003

[148] Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis. 2005; 41(11):1559-1568. doi: 10.1086/497832

[149] Harmath A, Németh B, Pócsi I, Majoros L, Pfliegler WP, Kovács R. Phylogenomic diversity of clinical Saccharomyces cerevisiae and the prevalence of probiotic-derived isolates in a tertiary care center in Hungary. Microbiol Spectr. 2025:e02750-25. doi: 10.1128/spectrum.02750-25

[150] Samiksha F, San Valentin EMD, Li G, Blazer M, McCormick TS, Ghannoum M. A Narrative Review on the Functional Applications, Safety, and Probiotic Characteristics of Pichia. Nutrients. 2025; 17(22):3594. doi: 10.3390/nu17223594

[151] Salminen MK, Rautelin H, Tynkkynen S, et al. Lactobacillus bacteremia, species identification, and antimicrobial susceptibility of 85 blood isolates. Clin Infect Dis. 2006; 42(5):e35-e44. doi: 10.1086/500214

[152] Nguyen Y, Sperandio V. Enterohemorrhagic E. coli (EHEC) pathogenesis. Front Cell Infect Microbiol. 2012; 2:90. doi: 10.3389/fcimb.2012.00090

[153] Bielaszewska M, Aldick T, Bauwens A, Karch H. Hemolysin of enterohemorrhagic Escherichia coli: structure, transport, biological activity and putative role in virulence. Int J Med Microbiol. 2014; 304(5-6):521-529. doi: 10.1016/j.ijmm.2014.05.005

[154] Sougioultzis S, Simeonidis S, Bhaskar KR, et al. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression. Biochem Biophys Res Commun. 2006; 343(1):69-76. doi: 10.1016/j.bbrc.2006.02.080

[155] Czerucka D, Dahan S, Mograbi B, Rossi B, Rampal P. Saccharomyces boulardii preserves the barrier function and modulates the signal transduction pathway induced in enteropathogenic Escherichia coli-infected T84 cells. Infect Immun. 2000; 68(10):5998-6004. doi: 10.1128/IAI.68.10.5998-6004.2000

[156] Badia R, Brufau MT, Guerrero-Zamora AM, et al. β-Galactomannan and Saccharomyces cerevisiae var. boulardii modulate the immune response against Salmonella enterica serovar Typhimurium in porcine intestinal epithelial and dendritic cells. Clin Vaccine Immunol. 2012; 19(3):368-376. doi: 10.1128/cvi.05532-11

[157] Badia R, Zanello G, Chevaleyre C, et al. Effect of Saccharomyces cerevisiae var. Boulardii and β-galactomannan oligosaccharide on porcine intestinal epithelial and dendritic cells challenged in vitro with Escherichia coli F4 (K88). Vet Res. 2012; 43(1):4. doi: 10.1186/1297-9716-43-4

[158] Martins FS, Dalmasso G, Arantes RM, et al. Interaction of Saccharomyces boulardii with Salmonella enterica serovar Typhimurium protects mice and modifies T84 cell response to the infection. PLoS ONE. 2010; 5(1):e8925. doi: 10.1371/journal.pone.0008925

[159] Martins FS, Vieira AT, Elian SD, et al. Inhibition of tissue inflammation and bacterial translocation as one of the protective mechanisms of Saccharomyces boulardii against Salmonella infection in mice. Microbes Infect. 2013; 15(4):270-279. doi: 10.1016/j.micinf.2012.12.007

[160] Ashida H, Mimuro H, Sasakawa C. Shigella manipulates host immune responses by delivering effector proteins with specific roles. Front Immunol. 2015; 6:219. doi: 10.3389/fimmu.2015.00219

[161] Jennison AV, Verma NK. Shigella flexneri infection: pathogenesis and vaccine development. FEMS Microbiol Rev. 2004; 28(1):43-58. doi: 10.1016/j.femsre.2003.07.002

[162] Tafazoli F, Zeng CQ, Estes MK, Magnusson K-E, Svensson L. NSP4 enterotoxin of rotavirus induces paracellular leakage in polarized epithelial cells. J Virol. 2001; 75(3):1540-1546. doi: 10.1128/JVI.75.3.1540-1546.2001

[163] Buccigrossi V, Laudiero G, Russo C, et al. Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes. PLoS ONE. 2014; 9(6):e99830. doi: 10.1371/journal.pone.0099830

[164] Calich VL, Pina A, Felonato M, Bernardino S, Costa TA, Loures FV. Toll-like receptors and fungal infections: the role of TLR2, TLR4 and MyD88 in paracoccidioidomycosis. FEMS Immunol Med Microbiol. 2008; 53(1):1-7. doi: 10.1111/j.1574-695X.2008.00378.x

[165] Jawhara S, Poulain D. Saccharomyces boulardii decreases inflammation and intestinal colonization by Candida albicans in a mouse model of chemically-induced colitis. Med Mycol. 2007; 45(8):691-700. doi: 10.1080/13693780701523013

[166] Fidan I, Kalkanci A, Yesilyurt E, et al. Effects of Saccharomyces boulardii on cytokine secretion from intraepithelial lymphocytes infected by Escherichia coli and Candida albicans. Mycoses. 2009; 52(1):29-34. doi: 10.1111/j.1439-0507.2008.01545.x

[167] Pontier-Bres R, Rampal P, Peyron J-F, Munro P, Lemichez E, Czerucka D. The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin. Toxins. 2015; 7(11):4455-4467. doi: 10.3390/toxins7114455

[168] Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A. Probiotic mechanisms of action. Ann Nutr Metab. 2012; 61(2):160-174. doi: 10.1159/000342079

[169] Buts J-P, Bernasconi P, Vaerman J-P, Dive C. Stimulation of secretory IgA and secretory component of immunoglobulins in small intestine of rats treated with Saccharomyces boulardii. Dig Dis Sci. 1990; 35(2):251-256. doi: 10.1007/BF01536771

[170] Gedek. Adherence of Escherichia coli serogroup 0 157 and the Salmonella Typhimurium mutant DT 104 to the surface of Saccharomyces boulardii. Mycoses. 1999; 42(4):261-264. doi: 10.1046/j.1439-0507.1999.00449.x

[171] Tasteyre A, Barc M-C, Karjalainen T, Bourlioux P, Collignon A. Inhibition of in vitro cell adherence of Clostridium difficile by Saccharomyces boulardii. Microb Pathog. 2002; 32(5):219-225. doi: 10.1006/mpat.2002.0495

[172] Rigothier M, Maccario J, Gayral P. Inhibitory activity of Saccharomyces yeasts on the adhesion of Entamoeba histolytica trophozoites to human erythrocytes in vitro. Parasitol Res. 1994; 80(1):10-15. doi: 10.1007/BF00932617

[173] Cusumano CK, Hultgren SJ. Bacterial adhesion--a source of alternate antibiotic targets. IDrugs. 2009; 12(11): 699-705.

[174] Stier H, Ebbeskotte V, Gruenwald J. Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan. Nutr J. 2014; 13(1):38. doi: 10.1186/1475-2891-13-38