A modified yeast probiotic developed to treat inflammatory bowel disease – sciencedaily

The world of microbes living in the human gut can have tremendous effects on human health. Many diseases, including inflammatory bowel disease (IBD), are linked to the balance of these microbes, suggesting that restoring the right balance could help treat the disease. Many probiotics – yeasts or live bacteria – currently on the market have been optimized through evolution in the context of a healthy gut. However, to treat complex conditions like IBD, a probiotic would need to perform many functions, including the ability to turn off inflammation, reverse damage, and restore the gut microbiome. Given all of these needs, researchers at Brigham and Women’s Hospital have developed a ‘designer’ probiotic – a carefully designed yeast that can induce multiple effects for the treatment of IBD. The preclinical results of their work are published in Natural medicine.

“We took yeast – the very yeast that’s used to make beer – and we gave it the ability to detect inflammation and secrete an anti-inflammatory molecule,” said corresponding author Francisco Quintana. , PhD, researcher in the Ann Romney Center for Neurological Diseases at Brigham. “We call this new platform ‘Y-bots’ (yeast robots) and see the potential here for developing therapies that can treat gut tissue disease and more.”

Previous research from the Quintana lab has helped shed light on the link between the gut and diseases that affect the brain, suggesting potential applications for engineering probiotics beyond IBD.

Quintana and his colleagues developed their probiotic using Saccharomyces cerevisiae, a species of yeast used in winemaking, baking and brewing. Using CRISPR / Cas9 gene editing technology, researchers introduced genetic elements capable of detecting inflammation and responding to it by secreting an enzyme capable of breaking down a key molecule involved in inflammation. The modified yeast can secrete different levels of the enzyme, depending on the amount of inflammatory signal present in a place in the intestine. This means that the probiotic can have a very localized response to inflammation. In mice, the modified yeast was successful in suppressing intestinal inflammation, reducing fibrosis, and restoring a balanced gut microbiome.

To bring this new therapeutic platform to focus on IBD and other diseases in humans, Quintana and his colleagues will need to conduct safety studies. They also plan to refine and further test the modified yeast to see if it can speed up tissue repair. Beyond IBD, the team plans to investigate the use of modified probiotics to treat a common side effect of cancer immunotherapy, colitis.

“We want to use the tools of synthetic biology to design what can be found in nature,” Quintana said. “By designing probiotics, our goal is to create more personalized, localized and highly controlled drugs for the treatment of diseases of the intestine and beyond.”

This work was supported by the National Institutes of Health (grants NS102807, ES02530, ES029136, AI126880), the National MS Society (RG4111A1), International Progressive MS Alliance (PA-1604-08459) and Natural Sciences Engineering Research Council of Canada ( NSERC 492911). Quintana and four co-authors have filed a patent for the use of modified yeasts to treat inflammation.

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Material provided by Brigham and Women’s Hospital. Note: Content can be changed for style and length.

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