Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease, 2021, Benjamin M Scott et al

Mij

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Abstract
Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal tract. Extracellular adenosine triphosphate (eATP) produced by the commensal microbiota and host cells activates purinergic signaling, promoting intestinal inflammation and pathology. Based on the role of eATP in intestinal inflammation, we developed yeast-based engineered probiotics that express a human P2Y2 purinergic receptor with up to a 1,000-fold increase in eATP sensitivity.

We linked the activation of this engineered P2Y2 receptor to the secretion of the ATP-degrading enzyme apyrase, thus creating engineered yeast probiotics capable of sensing a pro-inflammatory molecule and generating a proportional self-regulated response aimed at its neutralization. These self-tunable yeast probiotics suppressed intestinal inflammation in mouse models of IBD, reducing intestinal fibrosis and dysbiosis with an efficacy similar to or higher than that of standard-of-care therapies usually associated with notable adverse events. By combining directed evolution and synthetic gene circuits, we developed a unique self-modulatory platform for the treatment of IBD and potentially other inflammation-driven pathologies.

https://www.nature.com/articles/s41591-021-01390-x
 
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Extracellular adenosine triphosphate (eATP) produced by the commensal microbiota and host cells activates purinergic signaling, promoting intestinal inflammation and pathology.
We linked the activation of this engineered P2Y2 receptor to the secretion of the ATP-degrading enzyme apyrase, thus creating engineered yeast probiotics capable of sensing a pro-inflammatory molecule and generating a proportional self-regulated response aimed at its neutralization.

It's interesting. So they are saying extracellular ATP is the (or perhaps part of the) cause of IBD. And they can create yeast cells that sense the e-ATP and mop it up.

I wonder how firm that assertion that e-ATP causes IBD is. There's the question of why commensal microbiota and/or host cells are producing extracellular ATP, presumably at a level that is higher than normal. So, even if you have engineered yeast cells busily mopping up the e-ATP, maybe it keeps getting produced at abnormally high levels.

I vaguely recall the suggestion that over-production of extracellular ATP is involved in the pathology of ME/CFS.
 
Ron Davis discusses Metabolic Trap in yeast here:

"We inserted the Human IDO1 gene into Baker’s Yeast. This gene leads to the production of a chemical compound called Nicotinamide Adenine Dinucleotide (NAD), essential for yeast to grow. We eliminated all other ways for yeast to produce NAD. Under normal levels of Tryptophan, the yeast grows normally".

A different angle I guess.
 
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