Biomineralized ZIF‐8 Encapsulating SOD from Hydrogenobacter Thermophilus: Maintaining Activity in the Intestine and Alleviating Intestinal Oxidative Stress

Abstract Oxidative stress is a major factor leading to inflammation and disease occurrence, and superoxide dismutase (SOD) is a crucial antioxidative metalloenzyme capable of alleviating oxidative stress. In this study, a novel thermostable SOD gene is obtained from the Hydrogenobacter thermophilus strain (HtSOD), transformed and efficiently expressed in Escherichia coli with an activity of 3438 U mg −1 , exhibiting excellent thermal stability suitable for scalable production. However, the activity of HtSOD is reduced to less than 10% under the acidic environment. To address the acid resistance and gastrointestinal stability issues, a biomimetic mineralization approach is employed to encapsulate HtSOD within the ZIF‐8 (HtSOD@ZIF‐8). Gastrointestinal simulation results show that HtSOD@ZIF‐8 maintained 70% activity in simulated gastric fluid for 2 h, subsequently recovering to 97% activity in simulated intestinal fluid. Cell and in vivo experiments indicated that HtSOD@ZIF‐8 exhibited no cytotoxicity and do not impair growth performance. Furthermore, HtSOD@ZIF‐8 increased the relative abundance of beneficial microbiota such as Dubosiella and Alistipes , mitigated oxonic stress and intestinal injury by reducing mitochondrial and total reactive oxygen species (ROS) levels in diquat‐induced. Together, HtSOD@ZIF‐8 maintains and elucidates activity in the intestine and biocompatibility, providing insights into alleviating oxidative stress in hosts and paving the way for scalable production.