Gautam Hemlata, Ahmad Shaik Noor, Banaganapalli Babajan, Popowich Shelly, Chow-Lockerbie Betty, Ayalew Lisanework E, Mandal Rupasri, Wishart David S, Tikoo Suresh, Gomis Susantha
Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Microbiol. 2025 May 9;16:1581309. doi: 10.3389/fmicb.2025.1581309. eCollection 2025.
(CP) induced necrotic enteritis (NE) is an economically significant intestinal disease of broiler chickens. Identifying potential biological markers during the development of NE might facilitate early disease control measures. Therefore, the current study aimed to identify the metabolites and metabolic pathways changes associated with the onset of NE in serum and feces of CP-infected broiler chickens.
The protein content of the feed was abruptly altered from 20% to 28% using a well-established NE model before challenging the birds with CP. Then, we performed a targeted, fully quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) -based assay for analyzing the metabolomics profile of serum, feces, and jejunal contents in NE birds. The data were analyzed to understand the trend of metabolite distribution, relationships between metabolites and pathway impacts.
Birds with NE showed metabolic variations including lipids, amino acids, and organic acids, across all the biological samples analyzed. This variation was higher in serum samples (310/597 metabolites, 51.92%), compared to fecal (182/608 metabolites, 29.93%), and jejunal samples (125/607 metabolites, 20.59%). A robust statistical analysis of these metabolites identified 19 common metabolites, including butyric acid and histamine. Pathway analysis identified that six of them were enriched in key pathways, like tricarboxylic acid cycle (TCA cycle) (citric acid and cis-aconitic acid), glyoxylate and dicarboxylate metabolism (citric acid and cis-aconitic acid), arginine-proline metabolism (spermine and creatinine), butanoate metabolism (butyric acid), and histidine metabolism (histamine). These pathways were related to energy synthesis, nitrogen metabolism, and immune response in NE birds.
This study highlights metabolic differences in birds with NE and underscores butyric acid and histamine as potential early biomarkers for NE diagnosis. The upregulation of these metabolites across serum, jejunal and fecal samples reflects their local and systemic impacts on the disease. These biomarkers play key roles in several NE hallmark features, including gut barrier disruption, dysbiosis of microbes and tissue injury through immune system activation, and systemic inflammation. Future studies need to validate our findings across field conditions and different predisposing factors.
球虫（CP）诱发的坏死性肠炎（NE）是肉鸡一种具有重要经济意义的肠道疾病。在坏死性肠炎发展过程中识别潜在的生物标志物可能有助于早期疾病控制措施。因此，本研究旨在确定感染CP的肉鸡血清和粪便中与坏死性肠炎发病相关的代谢物及代谢途径变化。
在给鸡接种CP之前，使用成熟的坏死性肠炎模型将饲料中的蛋白质含量从20%突然提高到28%。然后，我们基于靶向、全定量液相色谱-串联质谱（LC-MS/MS）分析了坏死性肠炎鸡血清、粪便和空肠内容物的代谢组学特征。对数据进行分析以了解代谢物分布趋势、代谢物之间的关系以及途径影响。
在所有分析的生物样本中，患有坏死性肠炎的鸡表现出包括脂质、氨基酸和有机酸在内的代谢变化。与粪便样本（182/608种代谢物，29.93%）和空肠样本（125/607种代谢物，20.59%）相比，血清样本中的这种变化更高（310/597种代谢物，51.92%）。对这些代谢物进行的强有力统计分析确定了19种常见代谢物，包括丁酸和组胺。途径分析确定其中六种在关键途径中富集，如三羧酸循环（TCA循环）（柠檬酸和顺乌头酸）、乙醛酸和二羧酸代谢（柠檬酸和顺乌头酸）、精氨酸-脯氨酸代谢（精胺和肌酐）、丁酸代谢（丁酸）和组氨酸代谢（组胺）。这些途径与坏死性肠炎鸡的能量合成、氮代谢和免疫反应有关。
本研究突出了患有坏死性肠炎的鸡的代谢差异，并强调丁酸和组胺是坏死性肠炎诊断的潜在早期生物标志物。这些代谢物在血清、空肠和粪便样本中的上调反映了它们对该疾病的局部和全身影响。这些生物标志物在坏死性肠炎的几个标志性特征中起关键作用，包括肠道屏障破坏、微生物群落失调以及通过免疫系统激活导致的组织损伤和全身炎症。未来的研究需要在田间条件和不同的诱发因素下验证我们的发现。
