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Rapid adaptation of rumen epithelium to these metabolic shifts is essential to maintain homeostasis, but the transcriptional mechanisms underlying this adaptation remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We analyzed the temporal progression of gene expression and metabolomic profile in rumen papillae collected during low-grain feeding (LG) and one week after transitioning to a HG diet (HG1), or four weeks after (HG4) in cows classified as susceptible or resistant to SARA. RNA sequencing identified 955 differentially expressed genes (DEGs) across time points, revealing a biphasic adaptation pattern. Early responses (HG1) showed moderate transcriptional changes, while HG4 was characterized by substantial transcriptional remodeling. Pathway analysis indicated three major functional categories affected during adaptation: cellular stress response, metabolic adaptation, and protein processing. Notably, sterol biosynthesis genes showed transient upregulation at HG1 followed by downregulation at HG4, coinciding with morphological changes in rumen wall thickness and n-butyrate concentration in rumen fluid. Correlation analyses comparing gene expression patterns and metabolite level changes triggered by the dietary transition revealed potential links between metabolic and transcriptional adaptation. Of particular interest, valerate levels at HG1 correlated with genes involved in tissue remodeling at HG4, implying that valerate may contribute to delayed epithelial responses. Next, transcriptional differences between SARA-susceptible and SARA-resistant animals included genes related to inflammation, cell structure, and metabolism that persisted across all time points, suggesting underlying intrinsic differences in SARA susceptibility that are present before and persist during dietary challenge. Key genes consistently differentially under-expressed in SARA-susceptible animals,\n                      <jats:italic>CCDC196<\/jats:italic>\n                      and\n                      <jats:italic>MYO7B<\/jats:italic>\n                      , represent potential biomarkers for SARA predisposition. Finally, the SARA-resistant group showed a greater number of transcriptome-metabolome correlations, suggesting more coordinated epithelial responses to diet change compared to the SARA-susceptible group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings provide insights into the molecular mechanisms underlying rumen adaptation to HG diets and individual variation in SARA susceptibility, providing a basis for developing strategies to optimize dietary transitions in ruminant production systems.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40104-026-01352-8","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:01:19Z","timestamp":1772409679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional adaptation of rumen papillae to high-grain diet reveals distinct temporal phases and SARA susceptibility signatures"],"prefix":"10.1186","volume":"17","author":[{"given":"Kalina","family":"Duszka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequias","family":"Castillo-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hartinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Redmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Biber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana Muhammad","family":"Atif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Aigensberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Schwartz-Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Kvalem Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Dengler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Berthiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Reisinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qendrim","family":"Zebeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Kreuzer-Redmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"1352_CR1","doi-asserted-by":"publisher","first-page":"s399","DOI":"10.1017\/S1751731118001921","volume":"12","author":"JC Plaizier","year":"2018","unstructured":"Plaizier JC, Mesgaran MD, Derakhshani H, Golder H, Khafipour E, Kleen JL, et al. 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