Mystery of unique probiotic yeast solved

Researchers led by Professor Johan Thevelein (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 commercialised for treatment of diarrhoea 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 Professor 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 Professor 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 100 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.