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The common management practices of dairy calves leads to increased starch concentration in feed, which subsequently may cause rumen acidosis while on milk and during weaning. Until recently, few attempts were undertaken to understand the health risks of prolonged ruminal acidosis in post weaning calves. Resultantly, the molecular changes in the digestive tracts in post-weaning calves with ruminal acidosis remain largely unexplored. In this study, we investigated the liver transcriptome changes along with its correlation with the rumen microbial rRNA expression changes in young calves using our model of feed induced ruminal acidosis. In this model, new born calves were fed a highly processed, starch-rich diet starting from one week of age through 16 weeks. A total of eight calves were involved in this study. Four of them were fed the acidosis-inducing diet (Treated) and the rest of the four were fed a standard starter diet (Control). Liver and rumen epithelial tissues were collected at necropsy at 17 weeks of age. Transcriptome analyses were carried out in the liver tissues and rRNA meta-transcriptome analysis were done using the rumen epithelial tissues. The correlation analysis was performed by comparing the liver mRNA expression with the rumen epithelial rRNA abundance at genus level. Calves with induced ruminal acidosis had significantly lower ruminal pH in comparison to the control group, in addition to significantly less weight-gain over the course of the experiment. In liver tissues, a total of 428 differentially expressed genes (DEGs) (fold-change, FC ≥ 1.5; adjusted  P  ≤ 0.1) were identified in treated group in comparison to control. Biological pathways enriched by these DEGs included cellular component organization, indicating the impact of ruminal acidosis on liver development in young calves. Specifically, the up-regulated genes were enriched in acute phase response  (P  < 0.01), pyruvate metabolic process ( P  < 0.01) and proton-acceptors ( P  ≪ 0.001), indicating the liver’s response to feed induced acidosis at the transcriptome level. Twelve transferase activity related genes had significant correlation with rumen microbial rRNA expression changes. Among these genes, two up-regulated genes were reported with involvement in lipid metabolism in the liver, implying the direct effect of feed-induced acidosis on both the rumen microbial community and liver metabolism. Our study provides insight into the physiological remodeling in the liver resultant from the prolonged acidosis in post weaning calves, which may facilitate future RNA-seq based diagnosis and precision management of rumen acidosis in dairy calves.

Changes in meta-transcriptome of rumen epimural microbial community and liver transcriptome in young calves with feed induced acidosis