Engineering Escherichia coli nissle 1917 with lactonase ZHD101 alleviates zearalenone-induced intestinal disruption and reproductive toxicity in rat.

Zearalenone (ZEN), a prevalent mycotoxin contaminating cereals, poses significant health risks, including reproductive and intestinal toxicity. Developing effective strategies to mitigate its harmful effects is crucial for ensuring food and feed safety. This study reports the development of a recombinant probiotic, Escherichia coli Nissle 1917 expressing the lactonohydrolase ZHD101 (EcNzhd), and evaluates its efficacy in detoxifying ZEN in vitro and in vivo. The ZHD101 gene was introduced into EcN using molecular cloning, and ZEN degradation was quantified by HPLC. In a rat model of daily ZEN exposure (40 µg/kg), the therapeutic effects of oral EcNzhd administration were assessed by analyzing intestinal barrier integrity, gut microbiota composition, short-chain fatty acid (SCFA) levels, systemic inflammation, oxidative stress, and reproductive organ histopathology. In vitro, EcNzhd degraded 97.8% of ZEN (15 µg/mL) within 2 h. In vivo, EcNzhd administration significantly ameliorated intestinal barrier damage, corrected gut dysbiosis, and restored beneficial SCFA production. Furthermore, the treatment attenuated systemic inflammation and oxidative stress, and notably prevented ZEN-induced uterine and ovarian damage. In conclusion, the engineered probiotic EcNzhd demonstrates significant potential as a live biotherapeutic agent to counteract ZEN toxicity, thereby safeguarding animal health and enhancing food safety. Future work should focus on optimizing stability and dosage, and confirming cross-species efficacy to facilitate its translation into the feed and food industries.