Yeasts as probiotics: Mechanisms, outcomes, and future potential
Introduction
The human microbiome consists not only of bacterial species but also an abundance of fungal and archaeal species (Hoffmann et al., 2013). Studies on the interactions between resident the mycobiome and the rest of the microbiota and the host have revealed complex and multifaceted relationships. One of the key aspects of this discovery is that there are multiple fungal species involved in gastrointestinal homeostasis in human beings and other mammals. The Human Microbiome Project found that the most abundant genera of fungi in the human gut are Saccharomyces, Malassezia, and Candida in descending order of abundance (Nash et al., 2017), with eight out of 15 genera comprising ascomycetes and Saccharomyces comprising approximately 5–65% of observed fungi. Since fungi are harbored in the gut environment, it follows that some resident species might provide a symbiotic benefit to the human host. These benefits may exist in the form of modulating immunological homeostasis, adaptive immunity, or through the general maintenance of microbial homeostasis in the gut through specific interactions (Lai et al., 2019).
Probiotics are living microorganisms that have the potential to be beneficial to host organisms when administered at the correct dosage (Hill et al., 2014). Humans have benefitted from microorganisms in food in various forms throughout history. The benefits of including certain live microbes in food were first indirectly observed in the health effects of fermented foods, though the cause would have been almost certainly unknown at the time (Gogineni et al., 2013). While most well-characterized probiotic microbes are bacteria such as Bifidobacteria and Lactobacillus (Bermudez-Brito et al., 2012), certain yeasts have been shown to have health benefits across various studies (Czerucka et al., 2007).
The most common yeast with proposed probiotic effects is Saccharomyces boulardii. Also known as Saccharomyces cerevisiae var. boulardii or Saccharomyces cerevisiae Hansen CBS 5926, over-the-counter preparations of this yeast are typically recommended for the treatment of acute gastrointestinal diseases such as rotoviral and bacterial diarrhea (Kelesidis and Pothoulakis, 2012) and chronic conditions such as inflammatory bowel disease (Madsen, 2001). In this review, we describe several proposed probiotic mechanisms of this yeast and update readers on recent clinical and preclinical studies. Finally, we address a new frontier in the use of probiotics: the potential for the use of engineered yeast as live biotherapeutics.
Section snippets
Saccharomyces boulardii: A probiotic yeast
Saccharomyces strains have been observed in up to 96.8% of samples in recent mycobiome studies (Dollive et al., 2012, Nash et al., 2017). The prevalence of Saccharomyces strains in the human GI tract is not surprising since live S. cerevisiae and related species have been purposely consumed by humans for thousands of years in bread, beer, and other fermented foods and beverages. However, there are very few S. cerevisiae strains with demonstrated benefits to the host (Fernandez-Pacheco et al.,
Genetic differences between S. boulardii and S. cerevisiae
S. boulardii and S. cerevisiae are genetically very similar, each containing 16 chromosomes with greater than 99% relatedness by average nucleotide identity (Khatri et al., 2017). Some of the important differences include those in the genes expressing some flocculation proteins, which contribute to a different adhesion profile of S. boulardii when compared to S. cerevisiae (Edwards-Ingram et al., 2007). A major genetic difference between S. boulardii and other S. cerevisiae is chromosome IX
Heterologous gene expression
While some the qualities of S. boulardii make it an attractive probiotic, its efficacy could theoretically be improved by genetic engineering to amplify inherent benefits or add new probiotic characteristics. Previous work in the well characterized probiotic Escherichia coli Nissle 1917 has demonstrated the value that can be added to a probiotic through genetic engineering (Kurtz et al., 2018). In this study, the essential gene thymidylate synthase was deleted from the genome, resulting in a
Conclusion
S. boulardii is a probiotic yeast that has been shown to be useful in fighting various GI tract infections in rat models as well as human beings. This organism’s probiotic attributes largely stem from being able to modulate host immunity as well as the ability to competitively exclude pathogenic bacteria. S. boulardii is also suited for survival in mammalian hosts as compared to other yeasts. Preclinical and clinical studies have demonstrated the safety of using this yeast, with systemic
Acknowledgements
This work was supported by Iowa State University startup funds. TJM is partially supported by the Karen and Denny Vaughn Faculty Fellowship. The authors declare no conflict of interest. We thank Dr. Zengyi Shao for helpful discussions regarding this manuscript.
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