Rumen microbial dysbiosis is associated with productive lifespan decline in dairy cows via metabolic-inflammatory...

Gut microbiota has been established as a critical regulator of human longevity, but the mechanistic role of rumen microbiota in dairy cow productive lifespan remains unexplored. This study investigated differences in rumen microbial community structure and metabolic signatures in a longitudinal cohort of dairy cows with divergent productive lifespans, aiming to elucidate the correction and potential regulatory mechanisms governing dairy cow longevity through microbial-host metabolic reprogramming.

Our longitudinal study identified critical trends linked to increasing parity in dairy cows: milk yield and rumen microbiota diversity declined progressively, with microbial communities restructuring to show 37% higher abundance of Alphaproteobacteria and Pseudomonadota in cows with ≥ 4 parities compared to younger cohorts (parities 1-3). A key parity threshold was observed at the 4th lactation: early-parity cows (1-3) maintained energy-efficient metabolism via glycolysis/gluconeogenesis and TCA cycle, while ≥ 4th parity cows exhibited fundamental metabolic shifts-including altered methane-related gene expression, fermentation profile transitions from propionate- to acetate-dominated VFAs, and lipid dysregulation-alongside impaired nutrient conversion efficiency despite active B vitamin biosynthesis. These changes triggered pro-inflammatory metabolite accumulation, leading to systemic inflammation (elevated IL-1β/TNF-α/IL-6 levels) and reduced antioxidant capacity. Murine rumen microbiota transplantation experiments confirmed causality, with recipients of ≥ 4th parity microbiota developing gut barrier dysfunction and hepatic inflammation via TLR4/NF-κB pathway activation.

Longitudinal analyses classify rumen microbial dysbiosis as a potential driver of reduced productive longevity and lactation performance decline in dairy cows, suggesting that the temporal dynamics of the rumen microbiota influence lactation persistence and productive lifespan. This study fills the gap in microbiota-targeted strategies to extend dairy cows' productive longevity through precision microbial consortium modulation. Video Abstract.