A bioadhesive antioxidase-overexpressed probiotic prevents radiation enteritis by scavenging the excess reactive oxygen species.

IF 7.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Free Radical Biology and Medicine Pub Date : 2025-02-01 Epub Date: 2024-12-04 DOI:10.1016/j.freeradbiomed.2024.12.013
Ke Wang, Bochuan Yuan, Feng Zhang, Zhangyu Li, Xueli Jia, Yadan Hu, Ziyuan Chen, Jinyun Hong, Lina Du, Yiguang Jin
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Abstract

The scavenging of the excess reactive oxygen species (ROS) induced by radiation is fundamental for radiation protection. However, directly applying antioxidants results in low bioavailability and side effects. Superoxide dismutase (SOD) and catalase (CAT) have high ROS clearance efficiency, whereas their application is limited by the enzyme inactivation, making it difficult to exhibit significant therapeutic effects. Here, we engineered a probiotic Escherichia coli Nissle 1917 (EcN), i.e., AAEcN, serving as a SOD/CAT vehicle to scavenge ROS for the prevention and treatment of radiation enteritis (RE). The overexpressed Drsod and katE in AAEcN showed 5-fold ROS elimination efficiency compared to the wild EcN. Furthermore, the intestinal retention time of engineered EcN was prolonged through trefoil factor 3 gene (TFF3) modification of curli fibers on the bacterial surface, which contributed to the persistence of antioxidant enzyme activity. We found that AAEcN rapidly eliminated the intracellular ROS induced by radiation. Only a single oral dosing of AAEcN was satisfied to alleviate the radiation damage to the small intestine, colon, and spleen. Moreover, the homeostasis of pro-/anti-inflammatory cytokines was realized. The proliferation of the intestinal stem cells and spleen hematopoietic stem cells was enhanced, while the apoptosis of mucosal cells was inhibited. Our findings suggest valuable insights into the ROS scavenging way in RE, and establish an empirical basis for developing probiotics as an antioxidant enzyme vehicle for the bacteriotherapy of RE.

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一种生物黏附性抗氧化酶过度表达的益生菌通过清除过量的活性氧来预防放射性肠炎。
清除辐射引起的过量活性氧(ROS)是辐射防护的基础。然而,直接使用抗氧化剂会导致低生物利用度和副作用。超氧化物歧化酶(SOD)和过氧化氢酶(CAT)具有较高的ROS清除效率,但其应用受到酶失活的限制,难以表现出显著的治疗效果。在这里,我们设计了一种益生菌大肠杆菌Nissle 1917 (EcN),即AAEcN,作为SOD/CAT载体清除ROS,以预防和治疗放射性肠炎(RE)。与野生EcN相比,AAEcN中过表达的Drsod和katE的ROS消除效率提高了5倍。此外,通过对细菌表面卷曲纤维的三叶因子3基因(TFF3)修饰,延长了工程EcN的肠道滞留时间,从而保持了抗氧化酶的活性。我们发现AAEcN能迅速消除辐射诱导的细胞内ROS。仅口服一次剂量的AAEcN可减轻对小肠、结肠和脾脏的辐射损伤。此外,促/抗炎细胞因子实现了稳态。肠道干细胞和脾脏造血干细胞增殖增强,粘膜细胞凋亡受到抑制。我们的研究结果为研究RE中ROS的清除方式提供了有价值的见解,并为开发益生菌作为抗氧化酶载体用于RE的细菌治疗奠定了经验基础。
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来源期刊
Free Radical Biology and Medicine
Free Radical Biology and Medicine 医学-内分泌学与代谢
CiteScore
14.00
自引率
4.10%
发文量
850
审稿时长
22 days
期刊介绍: Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.
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