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The gut microbiome is formed by a vast and diverse community of bacteria that colonizes our large intestine. These bacteria start residing in the gut from birth and continue diversifying throughout life, influenced by factors such as diet, lifestyle, and stress. The gut bacterial community also includes bacteria from food and those that enter the colon through the anus.
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Prebiotics-Controlled Disposable Engineered Bacteria for Intestinal Diseases.

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Engineered bacteria can now record intestinal disease information and be destroyed on demand. This synthetic biology approach offers a disposable, recyclable solution for disease monitoring and treatment.

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Area of Science:

  • Synthetic biology
  • Microbial engineering
  • Gastroenterology

Background:

  • Intelligent engineered bacteria show promise for diagnosing and treating intestinal diseases.
  • A key challenge is safely managing engineered bacteria in vivo after their tasks are complete.

Purpose of the Study:

  • To develop thiosulfate-responsive engineered bacteria for disease monitoring and controlled elimination.
  • To create a system for recording disease information and enabling targeted drug delivery.

Main Methods:

  • Constructed engineered bacteria responsive to thiosulfate, an inflammatory bowel disease biomarker.
  • Utilized CRISPR/Cas9 base editing to generate sfGFP for monitoring and a lysisE gene mutation for recording.
  • Implemented a xylose-inducible system for engineered bacteria lysis and drug release.

Main Results:

  • The engineered bacteria successfully generated monitoring (sfGFP) and recording (lysisE mutation) signals.
  • Xylose addition induced lysisE expression, leading to bacterial destruction and AvCystain release.
  • Demonstrated a method for artificial attenuation and in situ drug release from engineered bacteria.

Conclusions:

  • Developed innovative engineered bacteria capable of recording real-time and historical disease data.
  • Engineered bacteria can be artificially attenuated and release drugs on demand, offering a disposable and recyclable therapeutic candidate.
  • This approach holds potential for various diseases, improving diagnosis, monitoring, and treatment strategies.