Arachidonic Acid Metabolism is Elevated in <i>Mycoplasma gallisepticum</i> and <i>Escherichia coli</i> 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 <i>Mycoplasma gallisepticum</i> (<i>MG</i>) and <i>Escherichia coli</i> (<i>E.coli</i>) 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.

家禽养殖业中频繁出现兼具高发病率与高死亡率的多种呼吸道疾病暴发疫情。代谢谱分析已被广泛应用于代谢性与感染性疾病研究，用于发掘生物标志物并解析复杂致病机制。本研究以血清样本中的鸡毒支原体（Mycoplasma gallisepticum, MG）与大肠杆菌（Escherichia coli, E.coli）共感染模型为对象，开展非靶向代谢组学（non-targeted metabolomics）分析，结果显示白三烯C4（Leukotriene C4, LTC4）、白三烯D4（Leukotriene D4, LTD4）、鹅脱氧胆酸盐、亚油酸盐及多种能量代谢物均发生显著变化。京都基因与基因组百科全书（KEGG）富集分析结果显示，亚油酸、牛磺酸与花生四烯酸（arachidonic acid, AA）相关代谢通路均呈上调趋势。为进一步阐明共感染的致病效应，本研究构建了包含代谢产物与酶基因的花生四烯酸代谢网络通路。结果显示，白三烯C4的水平呈极显著升高，且其变化与感染程度呈对应关系；与此同时，花生四烯酸代谢网络清晰呈现了多种呼吸道疾病暴发时该通路内各类代谢物的变化与差异特征。综上，共感染可通过激活花生四烯酸代谢通路，引发血清代谢组发生显著改变；此外，血清中的白三烯C4可作为检测家禽呼吸道疾病的潜在生物标志物。