Characterizing the impact of a novel therapeutic on the poultry gut microbiome

沙门氏菌感染是一个重大的公共卫生问题。感染源包括受污染的 肉、蛋和新鲜农产品。因此，控制家禽产品中的沙门氏菌感染是一项重要的 以减少人类感染。虽然在减少沙门氏菌的频率方面取得了进展， 在加工家禽中的污染，商业种植者面临越来越大的压力，以防止和/或 在收获前生产设施中消除这些病原体。NovoBind畜牧治疗公司提出 开发一种新的基于抗体的治疗剂，可以提供给商业种植者，以预防和/或 在收获前家禽生产设施中消除沙门氏菌。目前，新的沙门氏菌特异性 已经产生了抗体，并且正在测试它们在细胞培养中的功效。下一步需要 在收获前鸡群中测试体内功效。需要进行平行研究，以确定 这些治疗药物对家禽微生物组的影响。家禽的肠道微生物群对于维持 健康和防御病原体。必须证明这些抗体在给药时 在治疗水平，能够消除沙门氏菌，同时使正常家禽的其他成员 植物群完好。这项工作利用了Mohn实验室的微生物组分析专业知识， 将补充更大的研究团队的专业知识。本项目提出：（1）使用高通量 DNA测序和生物信息学分析，以表征和比较健康， 沙门氏菌感染和抗体治疗的家禽，（2）确定抗体治疗对 微生物组，（3）比较抗体递送疗法与传统疗法对微生物组的影响 目前用于控制沙门氏菌感染的基于抗生素的疗法。发展 沙门氏菌选择性治疗，对宿主生理和正常植物群的影响最小，将受益 通过消除食物链中的抗生素来源，同时减少 人类感染和疾病、生命损失和治疗费用。

Salmonella infections represent a significant public health concern. Sources of infection include contaminated meat, eggs, and fresh produce. As such, the control of Salmonella infections in poultry products is an important means to reduce human infections. While advances have been made in reducing the frequency of Salmonella contamination in processed poultry, there is mounting pressure on commercial growers to prevent and/or eliminate these pathogens in pre-harvest production facilities. NovoBind Livestock Therapeutics Inc. proposes to develop a novel antibody-based therapeutic that could be provided to commercial growers to prevent and/or eliminate Salmonella in pre-harvest poultry production facilities. Currently, novel Salmonella-specific antibodies have been generated and are being tested for their efficacy in cell culture. The next step requires testing efficacy in vivo in pre-harvest chicken flocks. Parallel studies are required to determine the impact of these therapeutics on the poultry microbiome. The intestinal microbiota in poultry is critical for maintenance of health and defense against pathogens. It is imperative to demonstrate that these antibodies, when administered at therapeutic levels, are capable of eliminating Salmonella while leaving other members of the normal poultry flora intact. This work capitalizes on the microbiome analysis expertise of the Mohn Laboratory, whose work will complement the expertise of the larger research team. This project proposes to: (1) use high-throughput DNA sequencing and bioinformatic analysis to characterize and compare the gut microbiome of healthy, Salmonella-infected and antibody-treated poultry, (2) determine any effects of antibody therapy on the microbiome, (3) compare the impact on the microbiome of antibody-delivered therapeutics versus traditional antibiotic-based therapies currently used to control Salmonella infection. Development of a Salmonella-selective therapeutic that has minimal effects on host physiology and normal flora, will benefit Canadians and worldwide populations by eliminating a source of antibiotics in the food chain while reducing human infection and illness, loss of life and costs of treatment.