Multi-omics revealed the mechanism of feed efficiency in sheep by the combined action of the host and rumen microbiota.

This study was conducted to investigate potential regulatory mechanisms of feed efficiency (FE) in sheep by linking rumen microbiota with its host by the multi-omics analysis. One hundred and ninety-eight hybrid female sheep (initial body weight = 30.88 ± 4.57 kg; 4-month-old) were selected as candidate sheep. Each test sheep was fed in an individual pen for 60 days, and the residual feed intake (RFI) was calculated. The ten candidate sheep with the highest RFI were divided into the Low-FE group, and the ten with the lowest RFI were divided into the High-FE group, all selected for sample collection. The RFI, average daily gain and average daily feed intake were highly significantly different between the two experimental groups ( < 0.05). Compared with Low-FE group, the insulin-like growth factor-1 and very low-density lipoprotein in serum and the propionate in rumen significantly increased in High-FE group ( < 0.01), but the acetate:propionate ratio in rumen significantly decreased in High-FE group ( = 0.034). Metagenomics revealed sp. and were key bacteria, and increased abundance of the genes encoding the enzymes for cellulose degradation and production of propionate in High-FE group. The results of proteomics and section showed the rumen papilla length ( < 0.001) and expression of carbonic anhydrase and Na/K-ATPase were significantly higher in High-FE group ( < 0.05). On the other hand, the acetyl-CoA content significantly increased in the liver of High-FE group ( = 0.002). The relative expression levels of insulin-like growth factor-1 and apolipoprotein A4 genes were significantly up-regulated in the liver of High-FE group ( < 0.01), but relative expression level of monoacylglycerol O-acyltransferase 3 gene was significantly down-regulated ( = 0.037). These findings provide the mechanism by which the collaborative interaction between rumen microbiota fermentation and host uptake and metabolism of fermentation products impacts feed efficiency traits in sheep.