Abstract
The average daily gain (ADG) is a critical index for evaluating growth rates in cattle and is closely linked to the economic benefits of the cattle industry. Heredity is one of the factors affecting the daily gain of cattle. However, the molecular mechanisms regulating ADG remain incompletely understood. This study aimed to systematically unravel the molecular mechanisms underlying the divergence in ADG between high average daily gain (HADG) and low average daily gain (LADG) Angus cattle through integrated multi-omics analyses (microbiome, metabolome, and transcriptome), hypothesizing that the gut microbiota-host gene-metabolism axis is a key regulatory network driving ADG divergence. Thirty Angus cattle were classified according to their HADG and LADG. Fecal and serum samples were collected for 16S, fecal metabolome, and blood transcriptome analysis. The results showed that compared with the LADG group, the abundance of Firmicutes increased in the HADG group, while the abundance of Bacteroidetes and Proteobacteria decreased. Metabolomics and transcriptomic analysis revealed that KEGG pathways associated with differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) were enriched in bile acid metabolism. Spearman correlation analysis showed that Oscillospira was positively correlated with ZBTB20 and negatively correlated with RADIL. ZBTB20 was negatively correlated with dgA-11_gut_group. This study analyzed the regulatory mechanism of average daily gain of beef cattle from genetic, metabolic, and microbial levels, providing a theoretical basis for analyzing the mechanism of differential daily gain of beef cattle, and has important significance for improving the production performance of beef cattle. The multi-omics network provides biomarker foundations for machine learning-based ADG prediction models, offering potential applications in precision breeding. While these biomarkers show promise for precision breeding, their causal roles require further validation. The conclusions are derived from a single breed (Angus) and gender (castrated males). Future studies should include females and diverse breeds to assess generalizability.