Discrepancies among healthy, subclinical mastitic, and clinical mastitic cows in fecal microbiome and metabolome and serum metabolome.

Mastitis is generally considered a local inflammatory disease caused by the invasion of exogenous pathogens and resulting in the dysbiosis of microbiota and metabolites in milk. However, the entero-mammary pathway theory may establish a possible link between some endogenous gut bacteria and the occurrence and development of mastitis. In the current study, we attempted to investigate differences in the gut microbiota profile and metabolite composition in gut and serum from healthy cows and those with subclinical mastitis and clinical mastitis. Compared with those of healthy cows, the microbial community diversities in the feces of cows with subclinical mastitis (SM) and clinical mastitis (CM) were lower. Lower abundance of Bifidobacterium, Romboutsia, Lachnospiraceae_NK3A20_group, Coprococcus, Prevotellaceae_UCG-003, Ruminococcus, and Alistipes, and higher abundance of the phylum Proteobacteria and the genera Escherichia-Shigella and Streptococcus were observed in CM cows. Klebsiella and Paeniclostridium were significantly enriched in the feces of SM cows. Several similarities were observed in feces and serum metabolites in mastitic cows. Higher levels of proinflammatory lipid products (20-trihydroxy-leukotriene-B4, 13,14-dihydro-15-keto-PGE, and 9,10-dihydroxylinoleic acids) and lower levels of metabolites involved in secondary bile acids (deoxycholic acid, 12-ketolithocholic acid), energy (citric acid and 3-hydroxyisovalerylcarnitine), and purine metabolism (uric acid and inosine) were identified in both SM and CM cows. In addition, elevated concentrations of IL-1β, IL-6, tumor necrosis factor-α and decreased concentrations of glutathione peroxidase and superoxide dismutase were detected in the serum of SM and CM cows. Higher serum concentrations of triglyceride and total cholesterol and lower concentrations of high-density lipoproteins in mastitic cows might be related to changes in the gut microbiota and metabolites. These findings suggested a significant difference in the profile of feces microbiota and metabolites in cows with different udder health status, which might increase our understanding of bovine mastitis.