{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:31:46Z","timestamp":1791379906738,"version":"4.3.3"},"reference-count":51,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central Government\u2019s Guiding Fund for Local Science and Technology Development","award":["23ZYQC0304"],"award-info":[{"award-number":["23ZYQC0304"]}]},{"name":"Central Government\u2019s Guiding Fund for Local Science and Technology Development","award":["24CXNA032"],"award-info":[{"award-number":["24CXNA032"]}]},{"name":"Central Government\u2019s Guiding Fund for Local Science and Technology Development","award":["Gaufx-04Y01"],"award-info":[{"award-number":["Gaufx-04Y01"]}]},{"name":"Science and Technology Project of Gansu Province\u2013Special Project for Cooperation between the Eastern and Western Regions","award":["23ZYQC0304"],"award-info":[{"award-number":["23ZYQC0304"]}]},{"name":"Science and Technology Project of Gansu Province\u2013Special Project for Cooperation between the Eastern and Western Regions","award":["24CXNA032"],"award-info":[{"award-number":["24CXNA032"]}]},{"name":"Science and Technology Project of Gansu Province\u2013Special Project for Cooperation between the Eastern and Western Regions","award":["Gaufx-04Y01"],"award-info":[{"award-number":["Gaufx-04Y01"]}]},{"name":"Fuxi Young Talents Program of Gansu Agricultural University","award":["23ZYQC0304"],"award-info":[{"award-number":["23ZYQC0304"]}]},{"name":"Fuxi Young Talents Program of Gansu Agricultural University","award":["24CXNA032"],"award-info":[{"award-number":["24CXNA032"]}]},{"name":"Fuxi Young Talents Program of Gansu Agricultural University","award":["Gaufx-04Y01"],"award-info":[{"award-number":["Gaufx-04Y01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress\/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic\u2013pituitary\u2013adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-\u03b1) within 1 day (p &lt; 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p &lt; 0.05), and oxidative damage (MDA levels doubled vs. CON; p &lt; 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune\u2013metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein\u2013protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects.<\/jats:p>","DOI":"10.3390\/ani15142135","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T14:03:51Z","timestamp":1752847431000},"page":"2135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impacts of Early Weaning on Lamb Gut Health and Immune Function: Short-Term and Long-Term Effects"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3802-1507","authenticated-orcid":false,"given":"Chong","family":"Li","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4832-5643","authenticated-orcid":false,"given":"Xiuxiu","family":"Weng","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Grassland Agro-Ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Peng","sequence":"additional","affiliation":[{"name":"Linxia Animal Husbandry Development Center, Linxia 731800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueming","family":"An","sequence":"additional","affiliation":[{"name":"Linxia Animal Husbandry Development Center, Linxia 731800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5242-7223","authenticated-orcid":false,"given":"Guoxiu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.applanim.2010.04.014","article-title":"Influence of weaning age and an experimental Haemonchus contortus infection on behaviour and growth rates of lambs","volume":"125","author":"Schichowski","year":"2010","journal-title":"Appl. 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