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Selenium and vitamin E are well-established antioxidant nutrients; but their combined regulatory effects via the rumen-liver axis remain insufficiently understood. To investigate this, twenty-four healthy lambs (average body weight: 20.39\u2009\u00b1\u20091.52\u00a0kg) were randomly assigned to four dietary treatment groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096 per group) and housed individually. The groups were as follows: a control (CON) group fed a basal diet; an SY group fed the basal diet supplemented with 0.6\u00a0mg\/kg selenium yeast (SY); a VE group fed the basal diet supplemented with 200\u00a0IU\/kg vitamin E (VE); and a MIX group fed the basal diet supplemented with both 0.6\u00a0mg\/kg SY and 200\u00a0IU\/kg VE. This study aimed to elucidate the underlying regulatory pathways of the rumen-liver axis by assessing lamb growth performance, immune function, antioxidant capacity, rumen fermentation parameters, and liver transcriptome profiles, and by analyzing the interrelationships among these variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lambs in the MIX group exhibited significantly higher average daily gain, serum concentrations of growth hormone and immunoglobulins, and enhanced serum antioxidant capacity compared to other groups (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Concurrently, the rumen environment was notably improved, characterized by reduced pH and ammonia\u2013nitrogen concentration, increased volatile fatty acid (VFA) production, and an elevated abundance of beneficial bacteria such as\u00a0Firmicutes\u00a0and\u00a0Prevotella. Liver transcriptomic analysis further revealed that differentially expressed genes (DEGs) were significantly enriched in pathways related to immune and antioxidant functions, notably arachidonic acid metabolism. Furthermore, correlation analysis suggested that rumen microbiota influence hepatic gene expression profiles through modulation of VFA metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings of this study demonstrate that the combined dietary supplementation of SY and VE enhances antioxidant and immune functions, and synergistically improves the growth performance and health status of lambs. These beneficial effects are closely associated with alterations in a \"rumen microbiota\u2013VFA\u2013liver\" axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-026-04785-3","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:25:09Z","timestamp":1773926709000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic regulation of selenium yeast and vitamin E on the rumen microbiota-VFA-liver axis in lambs"],"prefix":"10.1186","volume":"26","author":[{"given":"Shangwu","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengguo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"4785_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1080\/09712119.2021.1995392","volume":"49","author":"N Vera","year":"2021","unstructured":"Vera N, Guti\u00e9rrez C, Williams P. 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