{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:19:48Z","timestamp":1784204388504,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFE0124400"],"award-info":[{"award-number":["2023YFE0124400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024B03J1267"],"award-info":[{"award-number":["2024B03J1267"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Planning Project of Guangzhou","award":["2023YFE0124400"],"award-info":[{"award-number":["2023YFE0124400"]}]},{"name":"Science and Technology Planning Project of Guangzhou","award":["2024B03J1267"],"award-info":[{"award-number":["2024B03J1267"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Intestinal stem cells (ISCs) maintain epithelial renewal through their proliferation and differentiation capabilities, responding to various intestinal insults. However, the impact of iturin A, a natural antimicrobial peptide, on ISC viability and its potential to mitigate heat-stable enterotoxin b (STb)-induced intestinal damage remains unclear. Our recent study demonstrated that oral administration of iturin A enhances tight junction protein expression, accelerates crypt-villus regeneration, and restores epithelial barrier integrity in STb-exposed mice. Furthermore, iturin A promotes ISC proliferation and differentiation, significantly increasing the numbers of goblet and Paneth cells in the jejunum following STb exposure. Notably, iturin A regulates intestinal homeostasis by scavenging reactive oxygen species (ROS), while elevating total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) levels in both serum and jejunal mucosa. Mechanistically, iturin A facilitates nuclear factor-erythroid 2- related factor 2 (Nrf2) release by disrupting Kelch-like ECH-associated protein 1 (Keap1), leading to the upregulation of the antioxidant enzyme glutathione peroxidase 4 (GPX4). In conclusion, our findings indicate that iturin A alleviates oxidative stress induced by STb through modulation of the Keap1\/Nrf2 pathway and promotes ISC differentiation into goblet and Paneth cells, thereby enhancing resistance to STb-induced damage.<\/jats:p>","DOI":"10.3390\/antiox14040478","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T10:04:56Z","timestamp":1744797896000},"page":"478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Iturin A Potentiates Differentiation of Intestinal Epithelial Defense Cells by Modulating Keap1\/Nrf2 Signaling to Mitigate Oxidative Damage Induced by Heat-Stable Enterotoxin B"],"prefix":"10.3390","volume":"14","author":[{"given":"Geng-Xiu","family":"Zan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Zhan","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Liang","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run-Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Guang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Structural Biology, Nuffield Department of Medicine, Oxford University, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Chao","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Salvador-Erro, J., Pastor, Y., and Gamazo, C. 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