Differences in the composition of plasma metabolites and intestinal flora of piglets with different weaning weights revealed by untargeted metabolomics and 16S rRNA gene sequencing

Abstract BACKGROUND Piglets with different weaning body weights exhibit varying growth performance. This study explores the relationship between their plasma metabolites and gut microbiota to reveal differences in metabolic regulation and microbial composition. RESULTS Plasma and colon content samples from piglets of different weaning weights were collected. Untargeted metabolomics, 16S rRNA gene sequencing, multivariate statistics, and bioinformatics were used to identify and compare metabolites. Six key findings emerged. First, 23 differential metabolites were found, with three upregulated in high‐weight piglets and 20 downregulated in low‐weight piglets. A total of 15 were lipids or lipid‐like molecules. Second, metabolic pathway enrichment analysis indicated that the sphingolipid signaling pathway, HIF‐1 signaling pathway, sphingolipid metabolism pathway, ascorbate and aldarate metabolism pathway, and glycine, serine, and threonine metabolism pathway were the most significantly affected pathways in the plasma of piglets with different weaning body weights. Third, alpha diversity was lower in low‐weight weaned piglets. Fourth, Lactobacillus was 23.16% in high‐weight piglets, higher than 19.62% in low‐weight ones. Fifth, linear discriminant analysis effect size (LEfSe) analysis showed that Faecalibacterium is a biomarker for low‐body‐weight piglets and Oscillospira is a biomarker for high‐body‐weight piglets. Finally, Spearman correlation analysis indicated that Lactobacillus , Prevotella , Ruminococcus , and Oscillospira were negatively correlated with differential metabolites in plasma. CONCLUSION The plasma metabolites and colon microbiota differed between piglets of different body weights. Lipid‐related plasma metabolites contributed to weight variation, being lower in heavier piglets. The colonic microbiota, especially Oscillospira and Roseburia , exhibited strong correlations with these metabolites. © 2025 Society of Chemical Industry.