Dual-omics integration reveals microbial-metabolic signatures of bovine postpartum metritis

The precise interaction between the uterine microbiota and metabolites which lead to postpartum metritis remains poorly understood. The objective of this study was to conduct an exploratory integrative omics analysis to identify candidate associations between the microbiota and the metabolites in postpartum metritis of dairy cows. Blood and uterine contents were collected from metritis (n = 12) and health (n = 11, confirmed by further observation until 21 days postpartum) cows with the similar parity and body condition at 7 days postpartum. The analyses focused on the microbiota and the metabolites in the uterine contents. Utilizing 16S rRNA and metabolomics sequencing technology, we identified significant differences in the microbiota and metabolites between health cows and those with postpartum metritis. Whereafter, aiming to explore the comprehensive correlational landscape between the active metabolites and key pathogenic bacteria associated with postpartum metritis, we performed correlation analysis with the combination of the dual-omics.

At the phylum level, compared with the health group, the relative abundance of Bacteroidota and Fusobacteriota significantly increased, while Proteobacteria significantly decreased in the metritis group. At the genus level, the relative abundances of Porphyromonas, Bacteroides, Fusobacterium, Peptostreptococcus, Peptoniphilus-indolicus, Prevotella and Peptococcus significantly up-regulated, whereas Acinetobacter, Vibrio, Chryseobacterium, Elizabethkingia, Ralstonia, Burkholderia and Blautia down-regulated in the metritis group. Furthermore, a total of 20 annotated differential metabolites were screened out, with 11 up-regulated and 9 down-regulated metabolites in the diseased group. Among those differential metabolites, the increased abundance of PE(15_0/14_0), phloretic acid, succinic acid and PE(16_0/14_0) emerged as candidate predictors for the onset of postpartum metritis. Furthermore, Bacteroidota, Fusobacteriota and Proteobacteria also exhibited a strong positive correlation with PE(15_0/14_0), phloretic acid, succinic acid and PE(16_0/14_0). KEGG analysis further indicated that the postpartum metritis were correlated with the disorders of vital metabolic pathways such as propanoate metabolism, phenylalanine metabolism, and butanoate metabolism.

This study suggests that Bacteroidota, Fusobacteriota and Proteobacteria are correlated with the synthesis of distinct metabolites that may be adversely associated with metritis development in dairy cows. In summary, the observed microbial imbalances in the uterus of postpartum cows were accompanied by metabolic disorders, which could potentially caused the uterine damage. This study provides new insights and candidate biomarkers for further mechanistic investigation into postpartum metritis in cows.