02 July 2021

Theranostic yeast

Brewer's yeast revealed inflammation in the intestine and treated it

Anastasia Kuznetsova, N+1

American biologists have created genetically modified yeast that detects inflammation in the intestine, and then destroys pro-inflammatory molecules that trigger pathological reactions. Scientists tested such yeast on mice: intestinal inflammation decreased in animals, and their weight loss was less significant than in mice injected with ordinary yeast. The study was published in Nature Medicine (Scott et al., Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease).

The group of inflammatory bowel diseases includes ulcerative colitis and Crohn's disease. In patients suffering from these diseases, different parts of the intestine are affected, and pain, diarrhea and weight loss occur. Inflammation is associated with an inadequate immune response to intestinal bacteria. Predisposition to these diseases is determined by both genetic factors (impaired intestinal epithelial barrier and mucosal immune protection) and environmental factors, such as nutrition. For the treatment of inflammatory bowel diseases, immunosuppressants are used to suppress the pathological immune response of the body, but in many patients the disease does not respond to treatment with these drugs.

A team of scientists led by Francisco J. Quintana from Harvard Medical School has developed a new method for treating intestinal inflammation using genetically modified brewer's yeast. Biologists have hypothesized that if you turn extracellular ATP (eATP), which triggers a cascade of inflammatory reactions, into anti-inflammatory adenosine, it can reduce inflammation levels. At the same time, if there is too much adenosine, it can lead to fibrosis and even greater destruction of tissues, therefore, to control inflammation in the intestine, it is necessary to create a balance between extracellular ATP and adenosine. Scientists have created yeast Saccharomyces cerevisiae with a biosensor using the purine receptor P2Y2 to detect abnormal concentrations of extracellular ATP. Scientists connected the sensor with the enzyme apyrase, which breaks down extracellular ATP to adenosine.

The researchers tested the new method on mice in which intestinal inflammation was caused by 2,4,6-trinitrobenzenesulfonic acid. Scientists injected one group of mice (9 animals) with ordinary tremors, and the second group with genetically modified ones (9 animals). The condition of the mice was assessed by body weight, colon length (when the intestine is affected, it contracts) and histological picture. Those mice that received genetically modified yeast had a longer colon length (p = 0.0461) and lost less weight (p = 0.0010) than mice that were injected with conventional yeast.

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The effect of the use of genetically modified yeast (indAP) on inflammation of the colon. Ctrl – regular yeast, Ethanol – control.

Histological sections of the colon in mice treated with genetically modified yeast also showed a decrease in inflammation and fibrosis.

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Histological examination of the colon.

Genetically modified yeast is still at the preclinical stage of research, and it may take years before they are used in humans, but scientists are already thinking about how they can use developments in this area in the future. They plan to create genetically modified probiotics that will be able to diagnose intestinal diseases and immediately begin to treat them.

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