Arachidonic acid metabolism is elevated in Mycoplasma gallisepticum and Escherichia coli co-infection and induces LTC4 in serum as the biomarker for detecting poultry respiratory disease

Outbreaks of multiple respiratory diseases with high morbidity and mortality have been frequently reported in poultry industry. Metabolic profiling has showed widespread usage in metabolic and infectious disease for identifying biomarkers and understanding of complex mechanisms. In this study, the non-targeted metabolomics were used on Mycoplasma gallisepticum (MG) and Escherichia coli (E.coli) co-infection model in serum, which showed that Leukotriene C4 (LTC4), Leukotriene D4 (LTD4), Chenodeoxycholate, Linoleate and numerous energy metabolites were varied significantly. KEGG enrichment analysis revealed that the metabolic pathways of linoleic acid, taurine and arachidonic acid (AA) were upregulated. To further characterize the consequences of co-infection, we performed an AA metabolic network pathway with metabolic products and enzyme genes. The results showed that the expression of LTC4 increased extremely significant and accompanied with different degree of infection. Meanwhile, the AA network performed the changes and differences of various metabolites in the pathway when multiple respiratory diseases occurred. Taken together, co-infection induces distinct alterations in the serum metabolome owing to the activation of AA metabolism. Furthermore, LTC4 in serum could be used as the biomarker for detecting poultry respiratory disease. ABBREVIATIONS: MG: Mycoplasma gallisepticum; E.coli: Escherichia coli; AA: Arachidonic acid; LTC4: Leukotriene C4; CRD: chronic respiratory diseases; KEGG: Kyoto Encyclopedia of Genes and Genomes; LTs: leukotrienes; PGs: prostaglandins; NO: nitric oxide; HIS: histamine; PCA: Principal Component Analysis; PLS-DA: Partial Least Squares Discriminant Analysis; CCU: color change unit; UPLC: ultra-performance liquid chromatography; MS: mass spectrometry; DEMs: differentially expressed metabolites; ELISA: enzyme-linked immunosorbent assay; SD: standard deviation; VIP: Variable importance in the projection