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Porcine \u03b2-defensin 2 possesses excellent stability, making it an ideal antibiotic alternative for feed additives. In this study, a total of 15 piglets were used to investigate the effects of supplementing diets with 2.5 mg\/kg (LP group) and 5 mg\/kg (HP group) of pBD2 to weaned piglets. The results revealed that pBD2 significantly increased the total weight gain and average daily weight gain (p &lt; 0.05), the contents of T-AOC, SOD, IgM, and IL-10 in serum (p &lt; 0.05), the villus-to-crypt ratios, and the expression of tight-junction proteins ZO-1 and claudin-1 (p &lt; 0.05) in the small intestine. Furthermore, pBD2 increased the abundance of beneficial bacteria related to nutrient and energy metabolism while decreasing the abundance of harmful bacteria associated with intestinal inflammation and diarrhea. Alterations in the gut microbiota were closely associated with the levels of T-AOC, SOD, IgM, and IL-10 in serum. pBD2 primarily enhanced the health of weaned piglets by influencing antioxidant capacity, intestinal barrier function, and the intestinal microbiota. Our research provides a novel perspective for addressing the issue of antibiotic residues in feed.<\/jats:p>","DOI":"10.3390\/microorganisms13071443","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T13:13:04Z","timestamp":1750425184000},"page":"1443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effects of Recombinant pBD2 on the Growth Performance, Antioxidant Capacity, Immune Function, Intestinal Barrier, and Microbiota of Weaned Piglets"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-2237","authenticated-orcid":false,"given":"Zhanwei","family":"Teng","sequence":"first","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingke","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149205","DOI":"10.1016\/j.scitotenv.2021.149205","article-title":"A systematic review on antibiotics misuse in livestock and aquaculture and regulation implications in China","volume":"798","author":"Shao","year":"2021","journal-title":"Sci. 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