Metabolome of purulent materials of liver abscesses from crossbred cattle and Holstein steers fed finishing diets with or without in-feed tylosin.

Liver abscesses in feedlot cattle are a polymicrobial infection with Fusobacterium necrophorum and Trueperella pyogenes as the primary and secondary etiologic agents, respectively. Cattle with liver abscesses do not exhibit clinical signs and the abscesses are detected only at slaughter. The objective was to conduct metabolomics analysis of purulent materials of liver abscesses to identify biochemicals. Liver abscesses from crossbred cattle (n = 24) and Holstein steers (n = 24), each fed high-grain finishing diet with tylosin (n = 12) or no tylosin (n = 12), were included in the study. Abscess purulent materials were analyzed by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. A total of 759 biochemicals were identified and were broadly categorized into carbohydrates, energy metabolism pathways intermediates, peptides, amino acids and their metabolites, lipids and their metabolites, nucleotides, vitamins and cofactors, xenobiotics, and partially characterized molecules. The top 50 biochemicals identified included amino acids, lipids, nucleotides, xenobiotics, peptides, and carbohydrates and their metabolites. Among the 15 amino acid metabolites in the top 50 biochemicals, four were tryptophan metabolites, indoleacrylate, indolepropionate, tryptamine, and anthranilate. The 3-phenylpropionate, a product of phenylalanine metabolism, was the predominant metabolite in purulent materials. Between the four treatment groups, a two-way ANOVA analysis identified biochemicals that exhibited significant main effects for cattle type and in-feed tylosin use and their interactions. A total of 59 and 85 biochemicals were different (P < 0.05) between the cattle type (crossbred vs. Holstein steers) and in-feed tylosin use (tylosin vs. no tylosin), respectively. Succinate, an intermediate of lactate fermentation by some bacterial species, was one of the top 30 biochemicals that differentiated the four treatment groups. A number of lysophospholipids, indicative of bacterial and host cell membrane lyses, were identified in the purulent materials. In conclusion, to our knowledge this is the first report on the metabolome of liver abscess purulent materials and several biochemicals identified were related to metabolic activities of the bacterial community, particularly F. necrophorum and T. pyogenes. Biochemicals unique to liver abscesses that appear in the blood may serve as biomarkers and be of diagnostic value to detect liver abscesses of cattle before slaughter.

Liver abscesses in feedlot cattle, a consequence of feeding a diet of high-grain and low-roughage, are a mixed bacterial infection with Fusobacterium necrophorum, a ruminal bacterium as the primary causative agent. Cattle with liver abscesses do not exhibit clinical signs and the abscesses are detected only at slaughter. The study analyzed purulent materials of liver abscesses of feedlot cattle collected at slaughter for biochemical molecules. A total of 759 biochemicals were identified and a majority belonged to biochemical classes of lipids and amino acids and their metabolites. Biochemicals unique to liver abscesses that enter blood circulation may have the potential to be used as biomarkers in cattle with liver abscess before slaughter.

Hypoxic preconditioning protects against ischemic kidney injury through the IDO1/kynurenine pathway.

Prolonged cellular hypoxia leads to energetic failure and death. However, sublethal hypoxia can trigger an adaptive response called hypoxic preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia-inducible factors (HIFs) have been identified as key elements of oxygen-sensing machinery, the mechanisms by which hypoxic preconditioning protects against insults remain unclear. Here, we perform serum metabolomic profiling to assess alterations induced by two potent cytoprotective approaches, hypoxic preconditioning and pharmacologic PHD inhibition. We discover that both approaches increase serum kynurenine levels and enhance kynurenine biotransformation, leading to preservation of NAD+ in the post-ischemic kidney. Furthermore, we show that indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic increase of kynurenine and the subsequent renoprotection generated by hypoxic preconditioning and PHD inhibition. Importantly, exogenous administration of kynurenine restores the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our findings demonstrate a critical role of the IDO1-kynurenine axis in mediating hypoxic preconditioning.