Genome-resolved gut microbial guild and fecal metabolic signatures associated with post-weaning estrus return in sows.

Post-weaning estrus return is critical for sow reproductive efficiency. The gut microbiota is associated with post-weaning estrus of sows, potentially through effects on nutrient utilization and metabolic regulation. However, current microbial signatures associated with estrus return remain poorly resolved at the strain-level. Here, we explored the relationship between the gut microbiome and post-weaning estrus in sows using metagenomics and metabolomics profiling of 85 fecal samples. From 2,704 non-redundant metagenome-assembled genomes (MAGs), 608 estrus-associated MAGs were identified by LEfSe analysis. Among these, 48 high-quality MAGs were selected for co-abundance network analysis, which revealed two competing microbial functional guilds. Guild 1 was significantly enriched in the normal group, harboring more β-glucosidase and folate biosynthesis genes, but fewer antibiotic resistance genes and virulence factors than Guild 2. A random forest model based on these 48 MAGs demonstrated excellent performance in distinguishing between the normal and non-return sows (AUROC = 0.946) and was validated in an independent dataset (n = 29, AUROC = 0.818). Additionally, the guild-level microbiome index (GMI) derived from abundance differences between the two guilds also showed good discriminatory power (AUROC = 0.799). Integrated multi-omics analysis revealed alterations in fecal bile acid metabolism in non-return sows, characterized by a significantly increased ratio of secondary to primary bile acids and the accumulation of specific secondary bile acids. Notably, the enrichment of the Clostridia strain SFHK01 sp016296675, a member of Guild 2, and its encoded 12α-HSDH gene was positively associated with specific secondary bile acids, suggesting that this specific strain is involved in the distinct metabolic alterations observed in non-return sows. These findings provide the genome-resolved and guild-based insights into the gut microbial signatures associated with post-weaning estrus return, offering a basis for potential microbiota-targeted interventions to improve sow reproductive performance.