Researchers led by Prof. Johan Thevelein at the VIB-KU Leuven Center for Microbiology, have discovered that Saccharomyces boulardii, a yeast with probiotic properties, produces uniquely excessive amounts of acetic acid, the main component of vinegar.

They were able to find the genetic basis for this trait, which allowed them to abolish the acetic acid production of the yeast. If this unique S. boulardii trait can be further validated to have a probiotic effect in animal models, these results could provide the first scientific explanation for S. boulardii’s unique probiotic potency. The study is published in Genome Research.

A tale of mysterious yeast

In 1923 the French scientist Henri Boulard isolated a mysterious yeast strain from lychees in South East Asia. This yeast turned out to have unexpected and potent probiotic properties. This yeast, called Saccharomyces boulardii, has since been commercialized for treatment of diarrhea and other intestinal diseases. It is the only yeast strain that is prescribed as probiotic against gastrointestinal diseases and is now sold in pharmacies all over the world under a wide range of trade names, Enterol, Floratil, Sanifort, Génolevure, Ultralevure, Bioflor, Florastor and many others. It is also widely used as probiotic in animal nutrition.

Recent whole-genome DNA sequence analysis showed that S. boulardii is very closely related to the much better-known S. cerevisiae, the yeast species of which different varieties are commonly used in baking, beer brewing, wine making, bioethanol production, etc. The DNA sequence of these two yeasts is actually so similar that S. boulardii is no longer considered as a separate species but as a variety of S. cerevisiae. Why this S. boulardii yeast has been so successful as probiotic, as opposed to the common S. cerevisiae yeasts, has remained a complete mystery. It is even believed by some scientists to have more to do with superstition than with science.

The vinegar mutations

The team led by Prof. Johan Thevelein (VIB-KU Leuven) has now discovered that S. boulardii displays strong antibacterial activity as a distinguishable feature due to the production of unusually high levels of acetic acid, the main ingredient of vinegar. Acetic acid is a well-known preservative and strongly inhibits the growth of all microorganisms. But how does S. boulardii produce such large amounts of acetic acid?

Time for a genetic investigation, as Prof. Thevelein explains: "We were able to identify in more than eight years of tenacious research the genetic basis of this trait. We found two unique mutations in S. boulardii, that are responsible for the production of acetic acid. These mutations can act as a genetic ‘fingerprint’ that allows us to distinguish between these two types of yeast.”

The study thus reveals for the first time a genetic difference between S. boulardii and S. cerevisiae that can provide a scientific explanation for the superior probiotic potency of the former. This unique genetic signature will now, after nearly one hundred years, finally allow to isolate and identify with certainty new S. boulardii strains from nature.

Based on this knowledge, the researchers were able to implement CRISPR/Cas genome editing to abolish acetic acid production completely as well as switch high into very high acetic acid producers and vice versa. These modified yeast strains will now allow to test the importance of the acetic acid production for the probiotic power of S. boulardii in laboratory animals and for the first time establish a reliable scientific basis for the probiotic potency of S. boulardii. This, in turn, may pave the path towards improved treatments for intestinal diseases.

Publication

Offei B., P. Vandecruys, S. De Graeve, M.R. Foulquié-Moreno and J.M. Thevelein (2019) Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. boulardii. Genome research. In press.
DOI: 10.1101/gr.243147.118

View | Download | View article

Funding

This work was supported by an SBO grant (IWT 90043) from IWT-Flanders (now VLAIO-Flanders) and the EC 7th Framework program (CORNUCOPIA project) to JMT.
This research is part of a Grand Challenges project. The VIB Grand Challenges Program has been launched to significantly increase the societal impact of VIB, with support from the Flemish Government.

Questions from patients

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

About the VIB-KU Leuven Center for Microbiology

The big impact of bacteria on our health, the use of yeasts to enhance the production of chocolate, beer or bioethanol, yeast as a model system for studying human disease ... these are just a few of the research areas for the scientists at the VIB-KU Leuven Center for Microbiology. Their research also has important implications in various fields of application.

About VIB

Basic research in life sciences is VIB’s raison d’être. VIB is an independent research institute where some 1,500 top scientists from Belgium and abroad conduct pioneering basic research. As such, they are pushing the boundaries of what we know about molecular mechanisms and how they rule living organisms such as human beings, animals, plants and microorganisms. Based on a close partnership with five Flemish universities – Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel and Hasselt University – and supported by a solid funding program, VIB unites the expertise of all its collaborators and research groups in a single institute. VIB’s technology transfer activities translate research results into concrete benefits for society such as new diagnostics and therapies and agricultural innovations. These applications are often developed by young start-ups from VIB or through collaborations with other companies. This also leads to additional employment and bridges the gap between scientific research and entrepreneurship. VIB also engages actively in the public debate on biotechnology by developing and disseminating a wide range of science-based information.

About KU Leuven
KU Leuven is a leading European university dedicated to research, education and service to society. It is a founding member of the League of European Research Universities (LERU) and has a strong European and international orientation. Its sizeable academic staff conducts basic and applied research in a comprehensive range of disciplines. University Hospitals Leuven, its network of research hospitals, provides high-quality healthcare and develops new therapeutic and diagnostic insights with an emphasis on translational research. The University welcomes more 50,000 students from over 140 countries.Its doctoral schools organise internationally oriented PhD programmes for over 4,500 doctoral students.