{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T05:28:25Z","timestamp":1767245305844,"version":"3.48.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32560878"],"award-info":[{"award-number":["32560878"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004763","name":"Natural Science Foundation of Inner Mongolia Autonomous Region","doi-asserted-by":"crossref","award":["2024LHMS03054"],"award-info":[{"award-number":["2024LHMS03054"]}],"id":[{"id":"10.13039\/501100004763","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011811","name":"Inner Mongolia Agricultural University","doi-asserted-by":"crossref","award":["BR220133"],"award-info":[{"award-number":["BR220133"]}],"id":[{"id":"10.13039\/501100011811","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Compound yeast culture (CYC) is known to enhance animal health, but its effects on hepatic immune function are unclear. This study systematically examined CYC\u2019s regulatory effects on the liver of weaned lambs using transcriptomics and integrative bioinformatics. Ten lambs were randomly assigned to a control diet or a basal diet supplemented with 30 g\/d per head of Saccharomyces cerevisiae and Kluyveromyces marxianus co-culture (CYC group) for 42 days. Histological analysis showed that CYC improved hepatocyte arrangement and sinusoidal integrity, suggesting enhanced hepatic tissue stability. Cytokine analysis revealed CYC significantly increased IL-6 and IL-1\u03b2 while reducing IL-10, TGF-\u03b21, TNF-\u03b1, and CXCL9, indicating a bidirectional modulation of the immune response. Additionally, CYC enhanced antioxidant defenses by increasing T-SOD, GSH-Px, and T-AOC activities and decreasing MDA content. Transcriptomic sequencing indicated that CYC reshaped hepatic gene expression. Upregulated genes were enriched in immune-regulatory and structural pathways, including PI3K-AKT signaling, ECM\u2013receptor interactions, Toll-like receptor pathways, and cell adhesion molecules. Protein-level validation further confirmed activation of PI3K and AKTAKT phosphorylation with limited engagement of NF-\u03baB signaling. Conversely, downregulated genes were mainly associated with oxidative stress and energy metabolism, such as ROS-related pathways and MAPK signaling. WGCNA identified key hub genes (PTPRC, CD86, and ITGAV), which correlate with pro-inflammatory factors and participate in immune recognition, T-cell activation, and cell adhesion. These data suggest that CYC promotes hepatic immune homeostasis by enhancing immune signaling, stabilizing tissue architecture, and modulating oxidative stress\/metabolic processes. This study provides mechanistic insights into CYC\u2019s regulation of liver immune function and supports its targeted application as a functional feed additive for ruminants.<\/jats:p>","DOI":"10.3390\/ani16010104","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:30:52Z","timestamp":1767187852000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune-Modulatory Mechanism of Compound Yeast Culture in the Liver of Weaned Lambs"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8196-1482","authenticated-orcid":false,"given":"Chenlu","family":"Li","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Hohhot 010019, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5080-0313","authenticated-orcid":false,"given":"Pengxiang","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6674-2678","authenticated-orcid":false,"given":"Chenxue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dacheng","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Hohhot 010019, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Hohhot 010019, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jveb.2020.07.009","article-title":"Behavioral and physiological adjustments by lambs in response to weaning stress","volume":"41","author":"Mohapatra","year":"2021","journal-title":"J. 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