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This study established an immune stress model by intraperitoneal lipopolysaccharide (LPS) injection to investigate the mechanism by which Glycyrrhiza polysaccharides (GPs) alleviate LPS-induced immune stress. A total of 240 AA broilers were randomly assigned to four groups: control (CON), GP, LPS, and GP + LPS, with six replicates per group and ten birds per replicate. During the stress phase (28 d), LPS challenge increased serum ACTH and CORT concentrations and altered several immune-related parameters; whereas, GP supplementation improved ileal morphology and reduced serum IL-1\u03b2, NF-\u03baB, and TNF-\u03b1 concentrations. Significant GP \u00d7 LPS interactions were observed for IL-4, IgA, IgG, and iNOS. During the recovery phase (35 d), GP supplementation increased serum IgA and decreased iNOS, while significant GP \u00d7 LPS interactions were detected for IL-1\u03b2, NF-\u03baB, and sCD4. Notably, GP attenuated the LPS-associated increase in NF-\u03baB. Integrated multi-omics analysis indicated coordinated regulation at transcriptional and proteomic levels. GP upregulated FOS, JUN, and CATH3 and enriched NF-\u03baB and Wnt signaling at the transcript level, while increasing IRF1 and CATH3 and decreasing CTNNBIP1 at the protein level, primarily involving Wnt and MAPK pathways. Joint analysis identified CATH3 as a central regulatory target. Collectively, GP alleviates immune stress by restraining excessive inflammation and modulating Wnt\/MAPK signaling, thereby promoting intestinal structural recovery.<\/jats:p>","DOI":"10.3390\/ani16172633","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Transcriptomic and Proteomic Analyses Reveal the Effects and Mechanisms of Glycyrrhiza Polysaccharides in Alleviating Immune Stress in Broilers"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9164-589X","authenticated-orcid":false,"given":"Shuyan","family":"Wu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyi","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongying","family":"Weng","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhu","family":"Jin","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weize","family":"Qin","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8905-3947","authenticated-orcid":false,"given":"Haidong","family":"Du","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1742-6708","authenticated-orcid":false,"given":"Tiyu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103462","DOI":"10.1016\/j.psj.2024.103462","article-title":"Identification and Comparison of Aroma and Taste-Related Compounds from Breast Meat of Three Breeds of Korean Native Chickens","volume":"103","author":"Shin","year":"2024","journal-title":"Poult. 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