{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:07:33Z","timestamp":1779181653582,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011364","name":"Nutrients in Fermented Onion","doi-asserted-by":"publisher","award":["2025SKLANF-CAU2"],"award-info":[{"award-number":["2025SKLANF-CAU2"]}],"id":[{"id":"10.13039\/501100011364","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Laboratory of Animal Nutrition and Feeding"},{"name":"from Butuo Agricultural Investment Valley Breeding Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Feed additives play a crucial role in boosting livestock immunity, but their underlying molecular mechanisms are often incompletely understood. This study used integrated proteomics and metabolomics to systematically investigate the immunomodulatory effects of dietary fermented onion (FO) on the spleen of Liangshan Black Sheep. Results showed that FO supplementation significantly improved systemic antioxidant capacity and immune function, indicated by a higher spleen index and increased serum concentrations of SOD, MCP-1, and IL-2 (p &lt; 0.05). Multi-omics profiling of spleen tissues identified 169 differentially expressed proteins and 168 differential metabolites. Integrated pathway enrichment revealed calcium signaling and purine metabolism as potential core regulatory hubs for the observed immunomodulation. This molecular remodeling correlated with key molecules including protein F2R and metabolites adenosine and hypoxanthine, which may form a coordinated regulatory network. Overall, our findings suggest potential pathways linking dietary FO supplementation to enhanced splenic immune function in Liangshan Black Sheep, likely via synergistic regulation of specific signaling pathways. This work supports FO as a promising functional feed additive and provides a molecular framework for developing novel immunomodulatory strategies in livestock production.<\/jats:p>","DOI":"10.3390\/vetsci13050486","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:35:43Z","timestamp":1779176143000},"page":"486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Proteomics and Metabolomics Analysis Reveals Potential Pathways Underlying Onion-Mediated Regulation of Spleen Immune Function in Liangshan Black Sheep"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-4047","authenticated-orcid":false,"given":"Zengwen","family":"Huang","sequence":"first","affiliation":[{"name":"Xichang University, Xichang 615000, China"},{"name":"Xinjiang Taikun Group Co., Ltd., Changji 831100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Xichang University, Xichang 615000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiu","family":"Huang","sequence":"additional","affiliation":[{"name":"Xichang University, Xichang 615000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Lv","sequence":"additional","affiliation":[{"name":"Xinjiang Taikun Group Co., Ltd., Changji 831100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hehua","family":"Wang","sequence":"additional","affiliation":[{"name":"Xichang University, Xichang 615000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-7958","authenticated-orcid":false,"given":"Chaoyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Xichang University, Xichang 615000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengwang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Xichang University, Xichang 615000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiying","family":"Hao","sequence":"additional","affiliation":[{"name":"Xichang University, Xichang 615000, China"},{"name":"Panxi Laboratory of Animal Epidemic Disease Detection and Control of Sichuan, Xichang 615000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xichang University, Xichang 615000, China"},{"name":"Key Laboratory of Local Characteristic Goats, Xichang University, Xichang 615000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16756","DOI":"10.1038\/s41598-019-52995-9","article-title":"Identification and characterization of abundant repetitive sequences in Allium cepa","volume":"9","author":"Fu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Omar, A.E., Al-Khalaifah, H.S., Mohamed, W.A., Gharib, H.S., Osman, A., Al-Gabri, N.A., and Amer, S.A. (2020). Effects of Phenolic-Rich Onion (Allium cepa L.) Extract on the Growth Performance, Behavior, Intestinal Histology, Amino Acid Digestibility, Antioxidant Activity, and the Immune Status of Broiler Chickens. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.582612"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ochar, K., and Kim, S.H. (2023). Conservation and Global Distribution of Onion (Allium cepa L.) Germplasm for Agricultural Sustainability. Plants, 12.","DOI":"10.3390\/plants12183294"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.foodchem.2007.08.053","article-title":"Chemical composition, nutritional value and antioxidant properties of Allium caepa L. Var. tropeana (red onion) seeds","volume":"107","author":"Dini","year":"2008","journal-title":"Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.fct.2009.02.004","article-title":"Polyphenolics from various extracts\/fractions of red onion (Allium cepa) peel with potent antioxidant and antimutagenic activities","volume":"47","author":"Singh","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"374","DOI":"10.4314\/ajtcam.v9i3.11","article-title":"Effect of Allium cepa and Allium sativum on some immunological cells in rats","volume":"9","author":"Mirabeau","year":"2012","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19369","DOI":"10.3390\/ijms151119369","article-title":"Improved release and metabolism of flavonoids by steered fermentation processes: A review","volume":"15","author":"Camp","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/bies.20528","article-title":"Development and function of the mammalian spleen","volume":"29","author":"Brendolan","year":"2007","journal-title":"Bioessays"},{"key":"ref_9","first-page":"1709","article-title":"Research progress on structure, function and key immune genes of porcine spleen","volume":"47","author":"Song","year":"2020","journal-title":"China Anim. Husb. Vet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, C., Wang, S., Qi, Y., Jin, Y., Guan, R., and Huang, Z. (2025). Enhancing growth performance in Liangshan black sheep through fermented onion: Insights from transcriptomics and metabolomics. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1533728"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"Bronte","year":"2013","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4049\/jimmunol.180.1.171","article-title":"Loss of IL-7R and IL-15R expression is associated with disappearance of memory T cells in respiratory tract following influenza infection","volume":"180","author":"Shen","year":"2008","journal-title":"J. Immunol."},{"key":"ref_13","first-page":"977","article-title":"Transcriptomic analysis of thymus and spleen development in early-weaned yak calves supplemented with starter feed","volume":"35","author":"Hao","year":"2023","journal-title":"Chin. J. Anim. Nutr."},{"key":"ref_14","first-page":"2466","article-title":"Transcriptomic analysis of spleen and thymus development in early-weaned yak calves fed diets with different roughage sources","volume":"37","author":"Xu","year":"2025","journal-title":"Chin. J. Anim. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"eaau6085","DOI":"10.1126\/sciimmunol.aau6085","article-title":"Structure and function of the immune system in the spleen","volume":"4","author":"Lewis","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/j.1365-2621.2006.01268.x","article-title":"Effect of lactic acid fermentation of onions (Allium cepa) on the composition of flavonol glucosides","volume":"42","author":"Bisakowski","year":"2010","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Deng, J., Zhang, J., Chang, Y., Wang, S., Shi, M., and Miao, Z. (2022). Effects of Chinese yam polysaccharides on the immune function and serum biochemical indexes of broilers. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.1013888"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Metrani, R., Singh, J., Acharya, P., Jayaprakasha, G.K., and Patil, B.S. (2020). Comparative Metabolomics Profiling of Polyphenols, Nutrients and Antioxidant Activities of Two Red Onion (Allium cepa L.) Cultivars. Plants, 9.","DOI":"10.3390\/plants9091077"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Samota, M.K., Sharma, M., Kaur, K., Sarita Yadav, D.K., Pandey, A.K., Tak, Y., Rawat, M., Thakur, J., and Rani, H. (2022). Onion anthocyanins: Extraction, stability, bioavailability, dietary effect, and health implications. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.917617"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109033","DOI":"10.1016\/j.vetmic.2021.109033","article-title":"Effect of TMUV on immune organs of TMUV infected ducklings","volume":"255","author":"Zhang","year":"2021","journal-title":"Vet. Microbiol."},{"key":"ref_21","first-page":"33","article-title":"Effects of onion quercetin on immune organ index, macrophage phagocytic function and cytokine secretion in chickens","volume":"43","author":"Li","year":"2020","journal-title":"Feed. Res."},{"key":"ref_22","first-page":"45","article-title":"Effects of onion quercetin on meat quality, blood biochemistry and immune function of broilers","volume":"44","author":"Li","year":"2021","journal-title":"Feed. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.ijbiomac.2017.07.164","article-title":"Insights into physicochemical and functional properties of polysaccharides sequentially extracted from onion (Allium cepa L.)","volume":"105","author":"Zhu","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1111\/1750-3841.15415","article-title":"Effects of onion bulb processing conditions on drying characteristics, physicochemical and functional properties profile of onion (Allium cepa L.) powder","volume":"85","author":"Bamba","year":"2020","journal-title":"J. Food Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"132737","DOI":"10.1016\/j.foodchem.2022.132737","article-title":"Red onion skin active ingredients, extraction and biological properties for functional food applications","volume":"386","author":"Chadorshabi","year":"2022","journal-title":"Food Chem."},{"key":"ref_26","first-page":"486","article-title":"Effects of astragalus polysaccharides on growth performance, visceral organ indices and antioxidant capacity of 1\u201314 day-old broilers","volume":"23","author":"Wei","year":"2011","journal-title":"Chin. J. Anim. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yan, Z., Wang, K., Xia, B., Wu, J., and Chen, H. (2025). Development of Intelligent and Active Gelatin-Based Packaging Film Incorporating Red Onion Anthocyanins and Encapsulated Citronella Oil. Foods, 14.","DOI":"10.3390\/foods14193320"},{"key":"ref_28","first-page":"92","article-title":"Effects of onion quercetin on immunomodulatory function in immunosuppressed mice","volume":"45","author":"Ni","year":"2024","journal-title":"Food Ind."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/onc.2015.217","article-title":"Dysregulated protease activated receptor 1 (PAR1) promotes metastatic phenotype in breast cancer through HMGA2","volume":"35","author":"Yang","year":"2016","journal-title":"Oncogene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1158\/0008-5472.CAN-18-3206","article-title":"Thrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1-Dependent Immune Evasion","volume":"79","author":"Yang","year":"2019","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12959-019-0194-8","article-title":"Protease-activated receptors (PARs): Mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases","volume":"17","author":"Heuberger","year":"2019","journal-title":"Thromb. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"406","DOI":"10.2353\/ajpath.2008.070823","article-title":"Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy caused by PLA2G6 mutations","volume":"172","author":"Malik","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.2353\/ajpath.2009.090343","article-title":"Establishment of an improved mouse model for infantile neuroaxonal dystrophy that shows early disease onset and bears a point mutation in Pla2g6","volume":"175","author":"Wada","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Engel, L.A., Jing, Z., O\u2019Brien, D.E., Sun, M., and Kotzbauer, P.T. (2010). Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012897"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1212\/WNL.0b013e3181f73649","article-title":"Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism","volume":"75","author":"Yoshino","year":"2010","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.parkreldis.2015.01.012","article-title":"Homozygous p.D331Y mutation in PLA2G6 in two patients with pure autosomal-recessive early-onset parkinsonism: Further evidence of a fourth phenotype of PLA2G6-associated neurodegeneration","volume":"21","author":"Xie","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_37","first-page":"387","article-title":"Clinical significance of PIGN expression level in the treatment of glioma","volume":"19","author":"Wang","year":"2022","journal-title":"J. Clin. Neurosurg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29887","DOI":"10.18632\/oncotarget.15136","article-title":"PIGN gene expression aberration is associated with genomic instability and leukemic progression in acute myeloid leukemia with myelodysplastic features","volume":"8","author":"Teye","year":"2017","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/35055582","article-title":"Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation","volume":"409","author":"Demetriou","year":"2001","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7200","DOI":"10.4049\/jimmunol.173.12.7200","article-title":"N-acetylglucosaminyltransferase V (Mgat5)-mediated N-glycosylation negatively regulates Th1 cytokine production by T cells","volume":"173","author":"Morgan","year":"2004","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cell.2007.01.049","article-title":"Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation","volume":"129","author":"Lau","year":"2007","journal-title":"Cell"}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/5\/486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:23:45Z","timestamp":1779179025000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/5\/486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,17]]},"references-count":41,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["vetsci13050486"],"URL":"https:\/\/doi.org\/10.3390\/vetsci13050486","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,17]]}}}