Integrated multi-omics identifies dysregulated lipid metabolism of paresis in dairy sheep during the early transition period

Paresis during the early transition period is a prevalent metabolic disorder in prolific dairy sheep, characterized by a complex and poorly understood pathogenesis. This study longitudinally monitored a cohort of dairy sheep from 21 days antepartum to 1 day postpartum. During this period, blood, fecal, and colostrum samples were collected. The pathway of paresis was revealed by plasma metabolome and fecal 16S sequencing, and potential early biomarkers were identified. The physiological parameters of healthy dairy sheep (HDS) and paretic dairy sheep (PDS) differed in both the antepartum (not yet paresis) and postpartum (paresis) periods. Elemental analysis revealed higher levels of copper, potassium, and magnesium in PDS colostrum compared to HDS. Metabolomic analysis of HDS and PDS in antepartum identified 37 differential metabolites, with acylcarnitines (3-hydroxyhexadecadienoylcarnitine and 3-hydroxyoctanedioylcarnitine) emerging as promising early diagnostic biomarkers. 16S rRNA sequencing revealed distinct microbial signatures, with genera such as <i>Fusobacterium</i> and <i>Erysipelatoclostridium</i> enriched in PDS, whereas <i>Faecalibacterium</i> and <i>Bacillus</i> were more abundant in HDS. Integration of multi-omics data in postpartum revealed differences in glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glycine, serine and threonine metabolism, and primary bile acid biosynthesis between PDS and HDS. Our findings suggest that periparturient paresis in dairy sheep is linked to abnormal lipid and amino acid metabolism, with early potential biomarkers such as acylcarnitines identified. This study provides critical insights for developing strategies to prevent and manage periparturient paresis through targeted nutritional interventions and disease control.IMPORTANCEThis study investigates paresis in dairy sheep during the early transition period, identifying metabolic and physiological markers for early diagnosis. Longitudinal monitoring revealed prepartum differences in glucolipid profiles, liver enzymes, and oxidative stress markers between healthy and paretic sheep. Metabolomics identified 37 antepartum differential metabolites, including acylcarnitines, as potential biomarkers. Gut microbiota analysis revealed genera such as <i>Fusobacterium</i> and <i>Erysipelatoclostridium</i> enriched in paretic sheep, and <i>Faecalibacterium</i> and <i>Bacillus</i> in healthy individuals. Postnatal integration of multi-omics data revealed that paresis is closely associated with lipid metabolism and amino acid metabolism in dairy sheep. These findings support targeted nutritional strategies to mitigate periparturient metabolic disorders, enhancing dairy sheep health and productivity.