Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada.
Vaccinology and Immunotherapy, School of Public Health, University of Saskatchewan, 5D40 Health Sciences, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.
J Transl Med. 2024 Jan 19;22(1):80. doi: 10.1186/s12967-023-04728-w.
Necrotic enteritis (NE) is a severe intestinal infection that affects both humans and poultry. It is caused by the bacterium Clostridium perfringens (CP), but the precise mechanisms underlying the disease pathogenesis remain elusive. This study aims to develop an NE broiler chicken model, explore the impact of the microbiome on NE pathogenesis, and study the virulence of CP isolates with different toxin gene combinations.
This study established an animal disease model for NE in broiler chickens. The methodology encompassed inducing abrupt protein changes and immunosuppression in the first experiment, and in the second, challenging chickens with CP isolates containing various toxin genes. NE was evaluated through gross and histopathological scoring of the jejunum. Subsequently, jejunal contents were collected from these birds for microbiome analysis via 16S rRNA amplicon sequencing, followed by sequence analysis to investigate microbial diversity and abundance, employing different bioinformatic approaches.
Our findings reveal that CP infection, combined with an abrupt increase in dietary protein concentration and/or infection with the immunosuppressive variant infectious bursal disease virus (vIBDV), predisposed birds to NE development. We observed a significant decrease (p < 0.0001) in the abundance of Lactobacillus and Romboutsia genera in the jejunum, accompanied by a notable increase (p < 0.0001) in Clostridium and Escherichia. Jejunal microbial dysbiosis and severe NE lesions were particularly evident in birds infected with CP isolates containing cpa, netB, tpeL, and cpb2 toxin genes, compared to CP isolates with other toxin gene combinations. Notably, birds that did not develop clinical or subclinical NE following CP infection exhibited a significantly higher (p < 0.0001) level of Romboutsia. These findings shed light on the complex interplay between CP infection, the gut microbiome, and NE pathogenesis in broiler chickens.
Our study establishes that dysbiosis within the jejunal microbiome serves as a reliable biomarker for detecting subclinical and clinical NE in broiler chicken models. Additionally, we identify the potential of the genera Romboutsia and Lactobacillus as promising candidates for probiotic development, offering effective alternatives to antibiotics in NE prevention and control.
坏死性肠炎(NE)是一种严重的肠道感染,影响人类和家禽。它是由产气荚膜梭菌(CP)引起的,但疾病发病机制的确切机制仍不清楚。本研究旨在建立一种 NE 肉鸡模型,探讨微生物组对 NE 发病机制的影响,并研究具有不同毒素基因组合的 CP 分离株的毒力。
本研究在肉鸡中建立了 NE 的动物疾病模型。该方法包括在第一个实验中诱导突然的蛋白质变化和免疫抑制,在第二个实验中用含有不同毒素基因的 CP 分离株挑战鸡。通过对空肠的大体和组织病理学评分来评估 NE。随后,从这些鸟类收集空肠内容物进行 16S rRNA 扩增子测序的微生物组分析,然后进行序列分析,采用不同的生物信息学方法研究微生物多样性和丰度。
我们的研究结果表明,CP 感染,结合日粮蛋白质浓度的突然增加和/或感染免疫抑制型传染性法氏囊病病毒(vIBDV),使鸟类易患 NE 发展。我们观察到乳酸杆菌和 Romboutsia 属在空肠中的丰度显著降低(p<0.0001),而梭菌和大肠杆菌的丰度显著增加(p<0.0001)。与含有 cpa、netB、tpeL 和 cpb2 毒素基因的 CP 分离株相比,含有这些毒素基因的 CP 分离株感染的鸟类空肠微生物失调和严重的 NE 病变更为明显。值得注意的是,感染 CP 后未发生临床或亚临床 NE 的鸟类,Romboutsia 的丰度显著升高(p<0.0001)。这些发现揭示了 CP 感染、肠道微生物组和肉鸡 NE 发病机制之间的复杂相互作用。
我们的研究表明,空肠微生物组的失调可以作为检测肉鸡模型中临床和亚临床 NE 的可靠生物标志物。此外,我们发现 Romboutsia 和乳酸杆菌属具有作为益生菌开发的潜力,为 NE 的预防和控制提供了抗生素的有效替代方法。