Abstract Radiation enteritis is a common complication in patients undergoing abdominal radiotherapy. Current management strategies face significant limitations: clinical agents like amifostine are hindered by systemic side effects and demanding administration; direct supplementation with radioprotective metabolites such as propionate suffers from low bioavailability and transient action; and conventional probiotics lack targeted therapeutic output. To address these challenges, we engineered Escherichia coli Nissle 1917 to function as a living therapeutic that continuously produces and delivers propionate directly in the gut. This propionate-engineered probiotic achieved a production yield of 181.33 ± 4.27 mg/L in vitro. In a mouse model of abdominal irradiation, this engineered bacterium alleviated radiation-induced intestinal damage by continuously releasing propionate and enhancing intestinal epithelial barrier function. Multi-omics analysis revealed that the engineered bacterium could restore intestinal microbiota homeostasis, enhancing the abundance of advantageous bacteria with radioprotective properties (e.g., Dubosiella , Akkermansia ). Moreover, it modulated intestinal microbiota metabolism, influencing the metabolism of ascorbic acid, aldoses, and other metabolites. Additionally, it protected the intestinal mucosal barrier from radiation-induced damage, which was associated with the modulation of the SOCS1/JAK2/STAT3 signaling pathway. This study introduces a novel biological therapy to mitigate the side effects of radiotherapy and could open new avenues for preventing and treating radiation-induced intestinal injury.
Gao et al. (Tue,) studied this question.