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Soybean isoflavones (SIF) may modulate rumen fermentation, yet their effects on rumen function, microbiome features, host endocrine\/metabolic responses, and lactation performance-particularly across cows with divergent milk-yield phenotypes-remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty\u2011six lactating Holstein cows (28 high\u2011yield cows, HY; 28 low\u2011yield cows, LY) were divided into two categories by milk yield. Within each yield category, cows were randomly assigned to one of two dietary treatments: a basal diet (Control) or the basal diet supplemented with SIF at 0.01% of dry matter. This yielded a 2\u2009\u00d7\u20092 factorial design with four experimental groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914 per group): high\u2011yield control (HCON), high\u2011yield SIF (HSIF), low\u2011yield control (LCON), and low\u2011yield SIF (LSIF). SIF increased milk yield by 8.75% and improved fat-corrected milk (+\u20097.20%), dry matter intake (+\u20093.20%), and feed efficiency (+\u20093.26%), with larger gains in HY cows (milk yield\u2009+\u20098.89%; feed efficiency\u2009+\u20094.55%). Rumen fermentation shifted toward a more energetically favorable profile, with lower acetate (\u2013\u00a02.70%), higher propionate (+\u20094.55%), and a reduced acetate-to-propionate ratio (\u2013\u00a07.02%), accompanied by increased microbial crude protein (+\u200921.53%) without changes in pH or NH\n                      <jats:sub>3<\/jats:sub>\n                      -N. SIF altered endocrine status irrespective of phenotype, increasing estradiol and progesterone while decreasing prolactin and growth hormone, and reduced blood ALP, lactate, and triglycerides. Metagenomics indicated phenotype-dependent microbial and functional responses to SIF: HY cows showed enrichment of taxa (e.g.,\n                      <jats:italic>Caudoviricetes<\/jats:italic>\n                      sp\n                      <jats:italic>., Eubacterium<\/jats:italic>\n                      sp\n                      <jats:italic>.,<\/jats:italic>\n                      and\n                      <jats:italic>Butyrivibrio<\/jats:italic>\n                      sp\n                      <jats:italic>.<\/jats:italic>\n                      ) associated with amino-acid, cofactor metabolism and propionate pathways, whereas LY cows exhibited enrichment of\n                      <jats:italic>Prevotella<\/jats:italic>\n                      sp\n                      <jats:italic>.<\/jats:italic>\n                      and\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      sp\n                      <jats:italic>.<\/jats:italic>\n                      with functions favoring carbohydrate degradation. The HCON group exhibited greater abundances of\n                      <jats:italic>Prevotella<\/jats:italic>\n                      sp\n                      <jats:italic>.<\/jats:italic>\n                      and\n                      <jats:italic>Hallella<\/jats:italic>\n                      spp\n                      <jats:italic>.<\/jats:italic>\n                      with enhanced carbohydrate degradation functions, whereas the LCON group was enriched in\n                      <jats:italic>Ruminococcus<\/jats:italic>\n                      sp\n                      <jats:italic>.<\/jats:italic>\n                      and\n                      <jats:italic>Methanobrevibacter<\/jats:italic>\n                      sp\n                      <jats:italic>.<\/jats:italic>\n                      , associated with methane metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, this study highlights the potential of SIF supplementation to improve lactation efficiency, modulate rumen microecology and endocrine function in dairy cows. These findings establish a theoretical framework for achieving efficient and precise feeding management on large-scale dairy farms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40104-026-01397-9","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T03:01:12Z","timestamp":1778209272000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analysis of soy isoflavone-induced responses in rumen fermentation, endocrine status and milk production in cows with varying milk yields"],"prefix":"10.1186","volume":"17","author":[{"given":"Xingwei","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenguang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianrong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiarui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinfeng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengru","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"issue":"s2","key":"1397_CR1","doi-asserted-by":"publisher","first-page":"s220","DOI":"10.1017\/s1751731118001957","volume":"12","author":"I Mizrahi","year":"2018","unstructured":"Mizrahi I, Jami E. 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