Chapter 1
Chapter 2
Chapter 3

CONTENTS

1

Harnessing the Power of Probiotic Yeasts: Composition, Genome and Advantages over Bacteria
From Bread to Health: The Surprising Benefits of Probiotic Yeasts
Bacteria and Yeasts: Understanding the Distinctive Features of Two Powerful Microorganisms
The Genome: The Origin of All Differences
Survival: The Crucial Factor for Probiotic Effectiveness
Antibiotic-Resistance: A Unique Property of Yeasts

2

Diving Deep into the Distinct Mechanisms of Probiotic Yeast Strains
The 3-Layer Defense System of the Gut
S. cerevisiae var. boulardii and the Probiotic Activity in the Gut
S. cerevisiae var. boulardii and the Probiotic Activity on Immunity
S. cerevisiae CNCM I-3856: A New Generation of Probiotic Yeast
S. cerevisiae CNCM I-3856 and the Probiotic Activity on Immunity
S. cerevisiae CNCM I-3856: Its Particular Implication in Vaginal Health

3

Clinical evidence: Strain-specific Benefits of Probiotic Yeasts
S. cerevisiae var. boulardii: One of the Most Well-Documented Probiotics
Saccharomyces cerevisiae CNCM I-3856
S. cerevisiae CNCM I-3856 Beyond Gut Health: Advanced Studies on Women’s Health
S. cerevisiae CNCM I-3856: A Potential New Probiotic for Managing and Reducing Recurrence of Vulvovaginal Candidiasis
S. cerevisiae CNCM I-3856: Migration from the Intestine to the Vagina
Conclusion

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CHAPTER 1 | The Power of Probiotic Yeasts

Harnessing the Power of Probiotic Yeasts:
Composition, Genome and Advantages over Bacteria

From Bread to Health: The Surprising Benefits of Probiotic Yeasts

According to the World Health Organization (WHO), probiotics are “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.”¹ 1. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10. PMID: 24912386.  While lactic acid-producing bacteria (such as Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, and Enterococcus) dominate the probiotic market, yeasts are not lagging!

Yeast is a living, oval-shaped microorganism that has existed for hundreds of millions of years. Like bacteria, some yeasts are pathogenic—Candida albicans, for example, cause conditions like vaginal candidiasis—while others, such as Saccharomyces cerevisiae, may offer significant health benefits. Historically, this microorganism was domesticated by humans for food production because it can convert sugar (its primary nutrient) into alcohol and carbon dioxide.²2. What is Yeast? All you need to know about yeast – Explore Yeast But beyond baking bread and brewing wine, S. cerevisiae may also act as a powerful probiotic with notable health benefits.

This yeast strain is used in the prevention of various types of diarrhea, including antibiotic-induced and traveler’s diarrhea. Additionally, numerous preclinical and clinical studies have shown that S. cerevisiae var. boulardii plays supports the immune system.

However, other microorganisms belonging to the species S. cerevisiae have been intensively investigated over the last decade. Among these, the strain S. cerevisiae CNCM I-3856 is emerging as a new generation of probiotic yeast, showing beneficial properties, notably in relieving symptoms associated with IBS.

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Bacteria and Yeasts: Understanding the Distinctive Features of Two Powerful Microorganisms
Bacteria and yeasts, both single-celled microorganisms, share the fundamental characteristic of being unicellular organisms. However, they differ significantly in their cellular structure, properties, and organization. Yeasts are eukaryotic, meaning they have a well-defined nucleus containing the genetic material enclosed within a membrane, along with other membrane-bound organelles such as mitochondria. Eukaryotic cells also contain organelles like the endoplasmic reticulum and the Golgi apparatus.

In contrast, bacterial cells are prokaryotic, lacking a nucleus and possessing a simpler internal structure.

Yeasts are generally larger than bacteria, with a more complex cell wall composed of chitin and glucans, while bacterial cell walls are typically made of peptidoglycan and phospholipids. Additionally, yeasts reproduce asexually through budding, while bacteria divide through binary fission.

Comparative diagram of a bacterium (on the left) and a yeast (on the right)

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The Genome: The Origin of All Differences

DNA differences between yeasts and bacteria

Yeasts⁴4. 10 questions pour savoir si vous connaissez bien la levure ? – Tout sur la Levure and bacteria both possess DNA, the genetic material that carries the genetic code of these microorganisms, commonly referred to as the genome. This genome consists of both coding and non-coding regions. The coding regions, known as genes, enable these organisms to produce components of their membranes or proteins essential for metabolism, among other functions.

The major difference between these two microorganisms lies in the organization of their DNA. The DNA of yeast, located in its nucleus, consists of 16 pairs of chromosomes. In contrast, bacterial DNA is typically a single chromosome, often circular, and resides directly in the cytoplasm. DNA consists of base pairs organized into sequences that form the strands of this molecule. The greater the number of base pairs in a genome, the longer and typically more complex it becomes. To measure the size of a genome or a DNA sequence, we often use the unit “megabase,” which represents one million base pairs. The bacterial genome is also smaller, ranging from 0.5 to 15 megabases, while the yeast genome typically ranges from 10 to 20 megabases.

These significant genomic differences help explain why yeasts and bacteria differ so greatly. Even minor differences in DNA structure or genes can lead to substantial cellular and functional characteristic variations. What holds true between bacteria and yeast is also valid between two yeast strains within the same species, even though they share strong genetic homology. These differences, however minor, result in phenotypic and functional variations that account for the unique properties of each strain, as is the case with S. cerevisiae var. boulardii and S. cerevisiae CNCM I-3856.

Are All Saccharomyces Strains Genetically Identical?

For many years, it was believed that the yeast strains Saccharomyces cerevisiae and Saccharomyces boulardii were distinct. However, recent studies have shown that S. boulardii should be classified as a variant strain of S. cerevisiae,5. Edwards-Ingram L, Gitsham P, Burton N, Warhurst G, Clarke I, Hoyle D, Oliver SG, Stateva L. Genotypic and physiological characterization of Saccharomyces boulardii, the probiotic strain of Saccharomyces cerevisiae. Appl Environ Microbiol. 2007 Apr;73(8):2458-67. doi: 10.1128/AEM.02201-06. Epub 2007 Feb 9. PMID: 17293506; PMCID: PMC1855594. and it is now referred to as S. cerevisiae var. boulardii. In terms of morphology, the two strains are relatively similar, although S. cerevisiae var. boulardii is slightly more elongated than S. cerevisiae.

From a genetic point of view, S. boulardii CNCM I-3799 and S. cerevisiae CNCM I-3856 do not possess the same interdelta region profiles, which shows their structural differences at the DNA level.
Furthermore, they possess certain enzymes in common, while others differ, leading to variations in biological functions. For example, Saccharomyces cerevisiae can metabolize galactose, unlike the variant strain S. cerevisiae var. boulardii.6. Lesaffre internal documents

All these differences can explain why these two strains may be used differently as probiotics, displaying different actions on human health.

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Survival: The Crucial Factor for Probiotic Effectiveness

Probiotics are live microorganisms, and one of their key features in promoting health benefits is their ability to survive different environmental stresses during digestion. Survival assays of S. boulardii CNCM I-3799 and S. cerevisiae CNCM I-3856 have been conducted using an artificial model, the TIM-1 gastrointestinal system (TNO, Zeist, the Netherlands), which simulates the human upper gastrointestinal tract (stomach and small intestine). This dynamic, multi-compartmental model uses data collected from volunteer subjects to replicate the key factors of digestion as closely as possible to physiological reality. It mimics various parameters such as pH; body temperature; gastric dynamics; peristaltic mixing; transport along the tract; gastric, biliary, and pancreatic secretions; and the passive absorption of water and small molecules.

It has been demonstrated that the survival rates of these two strains are high in the upper gastrointestinal tract. Indeed, for both strains S. boulardii CNCM I-3799 and S. cerevisiae CNCM I-3856, the survival rate is until 95%.⁷ ⁹7. SURVIVAL OF LYNSIDE® PRO SCB IN THE IN VITRO GASTRO-INTESTINAL MODEL (TIM-1)
9. Blanquet-Diot S, Denis S, Chalancon S, Chaira F, Cardot JM, Alric M. Use of artificial digestive systems to investigate the biopharmaceutical factors influencing the survival of probiotic yeast during gastrointestinal transit in humans. Pharm Res. 2012 Jun;29(6):1444-53. doi: 10.1007/s11095-011-0620-5. Epub 2011 Nov 9. PMID: 22068280.

Due to their resistance to the gastric environment and bile acids, these two strains can reach the intestine and thus exert their beneficial effects on health. However, these effects are transient because these strains cannot colonize the colon in a lasting way.

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Antibiotic-Resistance: A Unique Property of Yeasts

Antibiotics are medications used to treat or prevent bacterial infections. They are, therefore, ineffective against yeasts or viruses. Antibiotics are classified as bactericidal if they directly kill bacteria, or bacteriostatic if they inhibit bacterial growth, preventing the infection from spreading and allowing the immune system to eliminate pathogenic bacteria.¹⁰

There are many classes of antibiotics, each with distinct characteristics:

In addition to these structural and mechanistic properties, antibiotics differ in their routes of administration (oral, intravenous, eye drops, creams, etc.), treatment duration, and contraindications.

Five classes are mainly used in therapy: beta-lactams, aminoglycosides, tetracyclines, quinolones, and macrolides.¹¹11. Calderón, Cassandra B., and Beulah Perdue Sabundayo. “Antimicrobial classifications.” Antimicrobial susceptibility testing protocols 7 (2007): 60-88. Most of these are broad-spectrum antibiotics, meaning their action is not targeted, so they destroy both pathogenic bacteria, responsible for infections, and beneficial bacteria, such as those constituting the human microbiota (skin, genital area, and especially the gut). This can cause dysbiosis¹²12. Etebu, Ebimieowei, and Ibemologi Arikekpar. “Antibiotics: Classification and mechanisms of action with emphasis on molecular perspectives.” Int. J. Appl. Microbiol. Biotechnol. Res 4.2016 (2016): 90-101, an imbalance or disruption in the composition and diversity of the microbiota. It causes numerous repercussions on the digestive system.

Although unicellular microorganisms like bacteria, yeasts are unaffected by antibiotics because they are eukaryotic and lack the therapeutic targets that antibiotics act upon. Therefore, probiotic yeasts can be taken alongside antibiotic treatments without compromising their efficacy. In particular, S. cerevisiae var. boulardii has been shown to help relieve antibiotic-associated diarrhea and restore the balance of gut microbiota.

References chapter 1

1. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10. PMID: 24912386.

2. What is Yeast? All you need to know about yeast – Explore Yeast

3. McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010 May 14;16(18):2202-22. doi: 10.3748/wjg.v16.i18.2202. PMID: 20458757; PMCID: PMC2868213.

4. 10 questions pour savoir si vous connaissez bien la levure ? – Tout sur la Levure

5. Edwards-Ingram L, Gitsham P, Burton N, Warhurst G, Clarke I, Hoyle D, Oliver SG, Stateva L. Genotypic and physiological characterization of Saccharomyces boulardii, the probiotic strain of Saccharomyces cerevisiae. Appl Environ Microbiol. 2007 Apr;73(8):2458-67. doi: 10.1128/AEM.02201-06. Epub 2007 Feb 9. PMID: 17293506; PMCID: PMC1855594.

6. Lesaffre internal documents

7. SURVIVAL OF LYNSIDE® PRO SCB IN THE IN VITRO GASTRO-INTESTINAL MODEL (TIM-1)

8. Cordonnier C, Thévenot J, Etienne-Mesmin L, Denis S, Alric M, Livrelli V, Blanquet-Diot S. Dynamic In Vitro Models of the Human Gastrointestinal Tract as Relevant Tools to Assess the Survival of Probiotic Strains and Their Interactions with Gut Microbiota. Microorganisms. 2015 Oct 23;3(4):725-45. doi: 10.3390/microorganisms3040725. PMID: 27682114; PMCID: PMC5023271.

9. Blanquet-Diot S, Denis S, Chalancon S, Chaira F, Cardot JM, Alric M. Use of artificial digestive systems to investigate the biopharmaceutical factors influencing the survival of probiotic yeast during gastrointestinal transit in humans. Pharm Res. 2012 Jun;29(6):1444-53. doi: 10.1007/s11095-011-0620-5. Epub 2011 Nov 9. PMID: 22068280.

10. Antibiotics – NHS. (n.d.). Antibiotics. Retrieved November 9, 2023, from https://www.nhs.uk/conditions/antibiotics

11. Calderón, Cassandra B., and Beulah Perdue Sabundayo. “Antimicrobial classifications.” Antimicrobial susceptibility testing protocols 7 (2007): 60-88.

12. Etebu, Ebimieowei, and Ibemologi Arikekpar. “Antibiotics: Classification and mechanisms of action with emphasis on molecular perspectives.” Int. J. Appl. Microbiol. Biotechnol. Res 4.2016 (2016): 90-101

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