Engineered <i>Bacillus subtilis</i> alleviates intestinal oxidative injury through Nrf2-Keap1 pathway in enterotoxigenic <i>Escherichia coli</i> (ETEC) K88-infected piglet.

Chaoyue Wen; Hong Zhang; Qiuping Guo; Yehui Duan; Sisi Chen; Mengmeng Han; Fengna LI; Mingliang Jin; Yizhen Wang

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Engineered Bacillus subtilis alleviates intestinal oxidative injury through Nrf2-Keap1 pathway in enterotoxigenic Escherichia coli (ETEC) K88-infected piglet.

Author: Chaoyue WEN ¹ ; Hong ZHANG ¹ ; Qiuping GUO ² ; Yehui DUAN ² ; Sisi CHEN ² ; Mengmeng HAN ² ; Fengna LI ² ; Mingliang JIN ³ ; Yizhen WANG ⁴
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1. Institute of Feed Science, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
2. Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China.
3. Institute of Feed Science, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. yzwang321@zju.edu.cn, mljin@zju.edu.cn.
4. Institute of Feed Science, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. yzwang321@zju.edu.cn.
Publication Type:Journal Article
Keywords: Engineered probiotics; Intestine; Nuclear factor-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway; Oxidative injury; Weaned piglets
MeSH: Animals; Swine; Enterotoxigenic Escherichia coli; Kelch-Like ECH-Associated Protein 1; Bacillus subtilis; NF-E2-Related Factor 2; Antioxidants; Oxidative Stress
From: Journal of Zhejiang University. Science. B 2023;24(6):496-509
CountryChina
Language:English
Abstract: Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties. In this study, we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32 (WB800-KR32) using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2 (Nrf2)‍-Kelch-like ECH-associated protein 1 (Keap1) pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli (ETEC) K88 in weaned piglets. Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet. The feed of the control group (CON) was infused with normal sterilized saline; meanwhile, the ETEC, ETEC+WB800, and ETEC+WB800-KR32 groups were orally administered normal sterilized saline, 5×10¹⁰ CFU (CFU: colony forming units) WB800, and 5×10¹⁰ CFU WB800-KR32, respectively, on Days 1‍‒‍14 and all infused with ETEC K88 1×10¹⁰ CFU on Days 15‍‒‍17. The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance, improved the mucosal activity of antioxidant enzyme (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased the content of malondialdehyde (MDA). More importantly, WB800-KR32 downregulated genes involved in antioxidant defense (GPx and SOD1). Interestingly, WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum. WB800-KR32 markedly changed the richness estimators (Ace and Chao) of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces. The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway, providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.