Feed additives as systems-level modulators of the ruminant host–microbiome interaction: a multi-omics perspective on efficiency, resistance, and reproduction

Ruminant livestock face converging pressures from climatic variation, antimicrobial agents, and the imperative for sustainable intensification. However, the molecular imprints through which nutritional interventions modulate host–microbiome interactions across physiological contexts remain fragmented across disciplinary themes. Here, we synthesize evidence from metagenomics, metatranscriptomics, metabolomics, and host transcriptomics to propose that feed additives operate as systems-level modulators of a functionally integrated rumen–liver–immune–reproductive axis, rather than acting on isolated metabolic pathways. Prevotella , Butyrivibrio , Ruminococcus , and Fibrobacter recurrently emerged across studies to be associated with feed efficiency, immune modulation, resistome dynamics, and reproductive fitness. However, their relationship is context dependent and not causal. Furthermore, hepatic transcriptomic and microRNA (miRNA)-mediated regulatory networks could serve as a molecular bridge connecting ruminal fermentation events to systemic phenotypic outcomes. The ruminant resistome may also represent a potential interface with public health rather than an isolated ecological phenomenon, given the capacity for horizontal gene transfer through mobile genetic elements, although the extent of transmission to humans remains to be quantified. Early-life microbial programming and reproductive tract microbiome composition also represent tractable intervention windows for precision management. This integrated framework could reframe feed additive research from a single pathway to a systems-level perspective, offering a basis for precision ruminant production.