IntroductionWith the goal to maximize intake of high-fermentable diet needed to meet energy needs during weaning period, calves are at risk for ruminal acidosis. Using the calves from previously established model of feed-induced, ruminal acidosis in young calves, we aimed to investigate the changes in rumen epimural transcriptome and its microbial metatranscriptome at weaning (8-week) and post-weaning (17-week) in canulated (first occurred at 3 weeks of age) Holstein bull calves with feed-induced subacute ruminal acidosis.MethodsEight bull calves were randomly assigned to acidosis-inducing diet (Treated, n = 4; pelleted, 42.7% starch, 15.1% neutral detergent fiber [NDF], and 57.8% nonfiber carbohydrates), while texturized starter was fed as a control (Control, n = 4; 35.3% starch, 25.3% NDF, and 48.1% nonfiber carbohydrates) starting at 1 week through 17 weeks. Calves fed acidosis-inducing diet showed significantly less (p < 0.01) body weight over the course of the experiment, in addition to lower ruminal pH (p < 0.01) compared to the control group. Rumen epithelial (RE) tissues were collected at both 8 weeks (via biopsy) and 17 weeks (via euthanasia) and followed for whole transcriptome RNA sequencing analysis. Differentially expressed genes (DEGs) analysis was done using cufflinks2 (fold-change ≥2 and p < 0.05) between treated and control groups at 8-week of age, and between 8- and 17-week for the treated group.ResultsAt 8-week of age, DEGs between treatment groups showed an enrichment of genes related to the response to lipopolysaccharide (LPS) (p < 0.005). The impact of prolonged, feed-induced acidosis was reflected by the decreased expression (p < 0.005) in genes involved in cell proliferation related pathways in the RE at 17-week of age in the treated group. Unique sets of discriminant microbial taxa were identified between 8-and 17-week calves in the treated group and the treatment groups at 8-week, indicating that active microbial community changes in the RE are an integral part of the ruminal acidosis development and progression.