Multi-omics profiling of gut-serum axis dynamics in gestational sows with different reproductive performance

ABSTRACT Sustainable swine production hinges on optimizing sow reproductive efficiency, yet mechanisms driving healthy litter size and weak piglet rates remain unclear. This study categorized sows into high (group H) and low (group L) healthy litter size groups based on median performance. Multi-omics analyses (16S rRNA sequencing, metagenomics, and serum metabolomics) revealed distinct fecal microbiota and metabolic profiles between groups. The results showed significant differences in microbiota composition between groups L and H. Group H exhibited a marked increase in Bacteroidetes abundance (particularly Prevotella sp . CAG1092 ), concurrent with reduced Firmicutes populations. Metabolomic analysis identified 197 differentially abundant metabolites, with 85 metabolites significantly enriched in group H. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that the differentially abundant metabolites were mainly involved in amino acid synthesis and metabolism, and multiple amino acid metabolic pathways were associated with polyamine synthesis. The correlation results showed a significant correlation ( P < 0.05) between these metabolites and litter size as well as litter weight. For instance, Prevotellaceae NK3B31 abundance positively correlated with L-alanine, urea, and securinine, while Prevotella sp . CAG1092 exhibited direct associations with reproductive performance. These findings suggest that gut microbiota dysbiosis may disrupt amino acid homeostasis and polyamine regulation, potentially serving as mechanistic links to reproductive efficiency. Reproductive performance dynamically shapes gut microbiota and systemic metabolism in gestating sows, with litter size influencing fecal metabolite diversity and microbial structure. This integrative analysis establishes a framework for improving both sow productivity and economic viability in pig farming. IMPORTANCE Optimizing sow reproductive efficiency is vital for sustainable swine production. This study identifies gut microbiota dysbiosis and metabolic imbalances as key drivers of litter size variability. Sows with lower productivity displayed marked reductions in Bacteroidetes (notably Prevotella spp.) and disrupted amino acid/polyamine metabolism, directly linking microbial shifts to poorer litter outcomes. Integrated multi-omics approaches revealed strong correlations between specific taxa ( Prevotella sp. CAG1092), metabolites (L-alanine and urea), and reproductive metrics, underscoring the gut-reproductive axis. These findings elucidate mechanistic connections between microbial ecosystems and host physiology, providing a foundation for targeted strategies like microbiota modulation or dietary interventions to enhance metabolic homeostasis and farrowing success. By bridging microbial ecology with livestock productivity, this work advances practical solutions to improve both animal health and agricultural profitability within precision farming frameworks.