Effects of synthetic breast milk on the gut metagenome and whole blood transcriptome in lambs

Early postnatal nutrition is crucial for the growth and development of lambs, and artificial milk formulas are widely used as alternatives to breast milk in intensive sheep production. However, the molecular and microbial mechanisms underlying the differences between breast milk and formula feeding remain unclear. This study aimed to compare the fecal metagenomic and whole blood transcriptomic profiles of lambs fed breast milk (BF group) and commercial formula (FF group) from 4 to 45 days of age, to provide a theoretical basis for optimizing formula compositions. A total of 6 lambs were randomly divided into two groups (n = 3 per group), with body weight and body dimensions measured at 45 days of age, followed by fecal metagenomic sequencing and whole blood transcriptomic sequencing. The results showed that BF lambs had significantly higher body weight, body length, heart girth, and chest width than FF lambs. Metagenomic analysis revealed that at the phylum level, Bacteroidetes was enriched in FF lambs, whereas Firmicutes predominated in BF lambs. Differential abundance was also observed at the genus level (higher Desulfovibrio in FF lambs) and the pathway level, with BF lambs enriched in quorum sensing and FF lambs showing higher abundances of pathways related to ubiquinone and other terpenoid-quinone biosynthesis. Moreover, transcriptomic analysis identified 3290 differentially expressed genes (DEGs) between the two groups, with DEGs mainly enriched in metabolic pathways, mTOR signaling pathway, osteoclast differentiation, B cell receptor signaling pathway and MAPK signaling pathway. Collectively, compared with FF, BF enhanced lamb growth, optimized gut microbiome structure and modulated blood transcriptomic profiles related to metabolism, signaling and immunity. These findings highlight the key microbial taxa and functional pathways modulated by breastfeeding, providing valuable insights for the development of more effective milk formula alternatives.