Microbiome by transcriptome interactions triggered by a switch to an alternative diet in Nellore cattle.

The interplay between diet and the microbiome in ruminants significantly influences livestock productivity and environmental sustainability. Among these effects, methane emissions—a potent greenhouse gas produced by rumen microbes—remain a major challenge, reinforcing the need for effective mitigation strategies. However, how dietary modifications reprogram microbial communities and their subsequent influence on host metabolism and methane production remains insufficiently understood. Here, we investigated the effects of diet on the ruminal and fecal microbiomes of young Nellore bulls, alongside host transcriptomic responses in key metabolic tissues, using a multi-tissue, diet-specific systems biology approach. Our gene co-expression and microbial co-abundance network analyses identified distinct microbial and transcriptomic signatures shaped by diet. Notably, Megasphaera and Butyrivibrio exhibited marked adaptations to dietary changes. Furthermore, methane emissions were associated with distinct sets of genes and microbial taxa depending on diet, with 42 genes and Eubacterium linked to methane in the traditional diet, whereas 18 distinct genes and Ruthenibacterium were associated with methane in the alternative diet. Our findings reveal an intricate, multifaceted, and diet-dependent interplay between microbiome composition, host gene expression, and metabolic processes, offering insights into microbial and molecular targets for optimizing livestock efficiency and sustainability.