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Octapeptin is a type of polypeptide with immunoregulatory activity. Therefore, the present study was conducted to investigate the effects of a novel octapeptin on growth performance, intestinal morphology, immune function, and serum metabolism in weaned piglets. A total of 240 21-d-old piglets with body weight (BW) of 7.06\u2009\u00b1\u20090.28\u2009kg were randomly assigned to five dietary treatments according to their initial BW and sex and fed a basal diet (CON) or a basal diet supplemented with octapeptin at 10, 20, 40, or 80\u2009mg\/kg (O10, O20, O40, and O80) respectively. Subsequently, eight piglets were selected from the CON group and the O80 group (superior growth performance), respectively, and slaughtered for further mechanistic investigation after 28-d feeding trial. Dietary octapeptin supplementation with 80\u2009mg\/kg significantly reduced the feed-to-gain (F\/G) ratio during d 15\u201328 (P\u2009&amp;lt;\u20090.01). Moreover, as the octapeptin level increased, the F\/G ratio decreased linearly across all growth phases, while BW during d 0\u201328 and average daily gain (ADG) over the entire period increased linearly (P\u2009&amp;lt;\u20090.05). Dietary supplementation with 80\u2009mg\/kg octapeptin (O80) significantly increased villus height and villus height-to-crypt depth ratio (P\u2009&amp;lt;\u20090.05). Furthermore, the O80 group exhibited significantly reduced levels of cytokines interferon-gamma (INF-\u03b3) and interleukin-6 (IL-6) in spleen (P\u2009&amp;lt;\u20090.05), increased mRNA expression of IL-10 in the ileal mucosa (P\u2009&amp;lt;\u20090.05), and decreased mRNA expression of IL-8 in mesenteric lymph nodes (P\u2009&amp;lt;\u20090.05). Serum metabolomics analysis demonstrated that dietary supplementation with O80 markedly altered the metabolic profile, enriching pathways associated with indole diterpene alkaloid biosynthesis, lysine biosynthesis and steroid biosynthesis. Our findings indicated that dietary supplementation with octapeptin could improve growth performance of weaned piglets, which was associated with linearly increased ADG and decreased F\/G ratio. Notably, dietary supplementation with O80 exhibited the optimal effect on growth performance, and further mechanistic analysis revealed that this octapeptin supplementation at this level enhanced ileum development, improved intestinal immune function, and modulated serum metabolism.<\/jats:p>","DOI":"10.1093\/jas\/skag179","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:45:48Z","timestamp":1782387948000},"source":"Crossref","is-referenced-by-count":1,"title":["Effects of dietary octapeptin supplementation on growth performance, intestinal morphology, immune function, and serum metabolism of weaned piglets"],"prefix":"10.1093","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9513-6932","authenticated-orcid":false,"given":"Bin","family":"Yang","sequence":"first","affiliation":[{"name":"College of Life Science and Agri-forestry, Southwest University of Science and Technology , Mianyang, 621010,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiebo","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Science and Agri-forestry, Southwest University of Science and Technology , Mianyang, 621010,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Science and Agri-forestry, Southwest University of Science and Technology , Mianyang, 621010,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Chongqing Academy of Animal Sciences , Chongqing, 402460,","place":["China"]},{"name":"Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs , Chongqing, 402460,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Crop Germplasm Resources (Institute of Biotechnology), Shandong Academy of Agricultural Sciences , Jinan, 250100,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Chongqing Academy of Animal Sciences , Chongqing, 402460,","place":["China"]},{"name":"Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs , Chongqing, 402460,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Life Science and Agri-forestry, Southwest University of Science and Technology , Mianyang, 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