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Xinran Gao1, Jiahao Wu1, Kaihua Ji2

  • 1School of Synthetic Biology and Biomanufacturing, State Key Laboratory of Synthetic Biology, Tianjin Key Laboratory of Biological and Pharmaceutical Engineering, Tianjin University, Tianjin, 300350, China.

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Engineered bacteria deliver propionate to combat radiation enteritis. This novel probiotic therapy protects the gut lining and restores microbial balance after abdominal radiotherapy.

Keywords:
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Area of Science:

  • Gastroenterology
  • Microbiology
  • Radiotherapy

Background:

  • Radiation enteritis is a common, debilitating side effect of abdominal radiotherapy.
  • Current treatments for radiation enteritis have significant limitations, including systemic side effects, poor bioavailability, and lack of targeted action.

Purpose of the Study:

  • To engineer a probiotic bacterium to continuously produce and deliver propionate in the gut.
  • To evaluate the efficacy of this engineered probiotic in mitigating radiation-induced intestinal damage.

Main Methods:

  • Engineered *Escherichia coli* Nissle 1917 to produce propionate.
  • Assessed propionate production in vitro.
  • Utilized a mouse model of abdominal irradiation to evaluate therapeutic effects.
  • Conducted multi-omics analysis to investigate mechanisms of action.

Main Results:

  • The engineered probiotic achieved a propionate yield of 181.33 mg/L in vitro.
  • In vivo, the engineered bacterium alleviated intestinal damage, enhanced epithelial barrier function, and restored gut microbiota homeostasis.
  • The therapy modulated microbial metabolism and protected the intestinal mucosal barrier via the SOCS1/JAK2/STAT3 pathway.

Conclusions:

  • Engineered *E. coli* Nissle 1917 serves as a novel living therapeutic for radiation enteritis.
  • This approach offers a promising strategy for preventing and treating radiation-induced intestinal injury by delivering propionate directly to the gut.