Host genetics shape productive lifespan in dairy cattle by sculpting rumen microbial metabolic functions

Background Rumen microbiota constitutes key determinants of productive lifespan in dairy cattle, a trait that lies at the heart of breeding program profitability. However, whether host genetic variation influences productive lifespan through its effects on the rumen microbiota remains largely unexplored. To address this, we generated and analyzed host genomic data, 16S rRNA sequences, metagenomic profiles, and longitudinal productive lifespan records from 333 dairy cows with divergent longevity. Results Rumen microbial community composition shifted significantly with increasing productive lifespan, characterized by a decline in firmicutes and an increase in proteobacteria , alongside reduced microbial diversity. We identified 28 core genera universally present across individuals and 113 keystone taxa through co-occurrence network analysis, which collectively represent functional hubs that may mediate host productive lifespan. Variance component analysis revealed substantial heritability in the rumen microbiome, with 82% of core genera and 87% of keystone taxa showing significant heritable signals. At the functional level, glycolysis/gluconeogenesis, quorum sensing, and the TCA cycle emerged as highly heritable pathways and exhibited strong genetic correlations with productive lifespan (|r_g| = 0.32–0.80). Productive lifespan itself was lowly heritable, yet the rumen microbiome explained 36.2% of its phenotypic variance-pointing to a major microbial contribution. Integrated microbiome-wide and genome-wide association studies identified four microbial genera and three host genetic variants significantly associated with productive lifespan. Multi-omics integration, combined with microbial genome assembly, further revealed that host genotypes influence productive lifespan indirectly through modulation of microbial metabolic pathways. Conclusions Integrating longitudinal multi-omics analyses, we uncovered a coordinated role for host genetics and rumen microbiota in regulating productive lifespan of dairy cattle, which lays the groundwork for genomically-informed, microbiome-targeted breeding strategies to enhance longevity, improve farm profitability, and support sustainable dairy production.