Tuning in to inflammation: A path forward for precise and efficacious microbiome medicines?

Area of Science:

• Microbiology and Synthetic Biology
• Gastroenterology and Immunology

Background:

• Gut microbes possess sensory capabilities adaptable for therapeutic interventions.
• Inflammatory conditions present unique cues that microbes can detect.
• Engineering microbial sensory circuits offers precise control over therapeutic responses.

Purpose of the Study:

• To engineer a synthetic gene circuit in yeast for fine-tuning extracellular ATP sensing.
• To evaluate the therapeutic potential of engineered microbes in preclinical models of intestinal inflammation.

Main Methods:

• Utilized directed evolution to optimize microbial sensing pathways.
• Developed a synthetic gene circuit in yeast to detect extracellular ATP.
• Tested the engineered yeast in murine models of chemical colitis and antibody-mediated enteritis.

Main Results:

• Successfully fine-tuned extracellular ATP sensing in engineered yeast.
• Demonstrated the therapeutic promise of the engineered yeast in preclinical models.
• Showcased the potential for scaled interventions targeting inflammatory pathways.

Conclusions:

• Engineered microbial sensory circuits can be precisely controlled.
• This approach offers a novel strategy for developing live biotherapeutics for inflammatory conditions.
• Further research can explore broader applications in gut health and disease management.