Abstract
BACKGROUND: The transition from a high forage to a highly fermentable diet can induce digestive disorders in the rumen. To date, the host mechanisms that regulate the adaption to such dietary transition are largely unknown. To understand the molecular mechanisms involved in such phenomena, RNA-sequencing was performed to identify the changes in the transcriptome of ruminal epithelia during gradual transition from a diet containing 0% to 89% grain. RESULTS: In total, the expression of 11,044, 11,322 and 11,282 genes were detected in ruminal epithelia of beef heifers (n = 15) fed 0%, 72% and 89% barley grain diet, respectively. The transcriptome profiles of rumen epithelia differed between low grain diet (LGD) (0% grain) and high grain diet (HGD) (72% and 89%), and HGD tended to reduce the expression of genes involved in epithelial catalytic and binding activities. When diet was changed from 72% to 89% grain, the mean ruminal pH change was significantly different among individual heifers with five of them decreased (down group (DG); from 6.30±0.09 to 5.87±0.15, P < 0.01) and five of them increased (up group (UG); from 5.84±0.42 to 6.35±0.37, P < 0.05). The functional analysis of differentially expressed (DE) genes revealed inhibited "Immune response of leukocytes", "Attraction of phagocytes", and "Cell movement of leukocytes" (P < 0.05) functions (Z-score = -2.2, -2.2 and -2.0, respectively) in DG, and inhibited "Concentration of lipid" and "Proliferation of epithelial cells" functions in UG (Z-score = -2.0, and -1.8, respectively). In addition, the expression of genes involved in ketogenesis (HMGCL) and lipid synthesis (SREBF2, FABP4) was increased in DG, while the expression of ketogenesis (ACAT2, HMGCS) and cholesterol synthesis related genes (HMGC and FDPS) were deceased in UG. Furthermore, the upstream regulators were found to be involved in the regulation of immune response and cell cycle progress, and SNP (g.46834311A > G) in FABP4 was identified between two groups of animals (P < 0.1). CONCLUSION: The identified genes, upstream regulators, and SNP could be potential genetic markers that may account for the varied individual ruminal pH responses to the dietary transition stress.