Improvements in feed efficiency often involve alterations in nutrient metabolism mediated by gastrointestinal microorganisms. These microorganisms serve as carriers of antibiotic resistance genes (ARGs); therefore, metabolic changes may influence the dissemination of ARGs. In this study, we investigated the variations in gastrointestinal ARGs between female Holstein calves exhibiting low residual feed intake (LRFI) with high feed efficiencies and those exhibiting high residual feed intake (HRFI) with low feed efficiencies. Metagenomics was conducted to analyze the underlying factors driving these differences. The LRFI calves exhibited 16.6 % higher ruminal ARG abundance but had reduced fecal ARG diversity. The abundance of Erysipelotrichaceae enrichment in LRFI rumen drove resistance functions and elevated carbohydrate-active enzymes (CAZymes) expression. Correlation analysis linked LRFI rumen enriched bacteria Erysipelotrichaceae and Coprobacillaceae to CAZymes, which were positively associated with multidrug, fluoroquinolone, and MLS resistance functions. Weighted Gene Co-Expression Network Analysis confirmed these resistance functions were dominant in LRFI calves. CAZymes improved substrate utilization, enhanced bacterial efflux resistance, promoted bacterial proliferation, and upregulated resistance genes. Rumen microbes and their resistomes systemically alter microbiota and ARG profiles in the feces. The contributions of fecal microbial abundance and diversity, mobile genetic elements (MGEs), and starch to the differences in ARGs were 14.92 %, 11.18 %, 8.90 %, and 10.25 %, respectively. In summary, LRFI calves require more CAZymes to reshape gut microbiota and ARG carrier populations, which lead to shifts in gastrointestinal ARG abundance/diversity shifts.
