Effects of lubabegron fumarate on ruminal fermentation and microbial community in a rumen simulation system

The expansion of the global beef industry intensifies concerns regarding ammonia emissions, posing a significant challenge to environmental sustainability and production efficiency. Lubabegron fumarate (LBF), a novel β-adrenergic receptor modulator approved to mitigate these emissions, lacks a defined ruminal mode of action. This study aimed to characterise the effects of LBF on in vitro rumen fermentation, microbial ecology, and nitrogen metabolism.

Using a rumen simulation system, we evaluated the effects of LBF on fermentation parameters, nutrient digestibility, and urease activity. To elucidate the underlying mechanisms, an integrated multi-omics approach was employed to characterise shifts in microbial community structure, functional potential, and metabolic output, with a specific focus on nitrogen-cycling microbiota.

LBF did not directly inhibit urease. Instead, it optimised the rumen microenvironment by increasing total volatile fatty acids and pH, while reducing ammonia nitrogen (NH₃-N) and enhancing starch digestibility. Crucially, LBF orchestrated a selective enrichment of key taxa (e.g., Ruminococcus_E, specific Prevotella spp.) and promoted pivotal pathways (e.g., starch metabolism and amino acid biosynthesis) without eroding microbial diversity. Metabolomics revealed a redirected carbon flux towards propionic acid production, facilitating efficient microbial nitrogen assimilation and redirecting nitrogen from ammonia into microbial protein (MCP).

LBF reshaped the rumen microecosystem to synchronise carbohydrate fermentation and nitrogen assimilation, thereby optimising nutrient capture and reducing nitrogen waste. These findings provide a mechanistic basis for the strategic application of LBF as a pharmaceutical intervention to improve nitrogen efficiency and mitigate ammonia emissions in cattle production.