Campylobacter jejuni restriction by the intestinal microbiota

空肠弯曲菌受肠道微生物群的限制

• 批准号: 10734573
• 负责人: Jorge E Galan
• 金额: $ 25.13万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734573
• 关键词: Animal Model; Animals; Antibiotics; Birds; Campylobacter jejuni; Chicken Model; Chickens; Clinical; Collection; Communities; Complication; Data; Development; Diarrhea; Disease Outbreaks; Domestic Animals; Domestic Fowls; Escherichia coli O157:H7; Farm; Food Chain; Food Industry; Foundations; Genes; Genetic Screening; Germ-Free; Growth; Guillain Barré Syndrome; Human; In Vitro; Individual; Infection; Intestines; Laboratories; Mediating; Modeling; Nerve Degeneration; Pathogenicity; Pathology; Patients; Phenotype; Physiological; Predisposition; Public Health; Reporting; Resistance; Role; Salmonella; Salmonella enteritidis; Salmonella typhimurium; Sampling; Shigella; Source; Symptoms; United States; Virulence Factors; Wild Animals; Work; base; combat; cost; diarrheal disease; dysbiosis; enteric pathogen; experimental study; foodborne; foodborne illness; gut colonization; gut inflammation; gut microbiota; healthy volunteer; immunological status; insight; microbial community; microbial composition; microbiota; novel strategies; pathogen; pathogenic bacteria; permissiveness; prevent; public health relevance; rRNA Genes; stool sample

PROJECT DESCRIPTION Campylobacter jejuni is the most common cause of food-born diarrhea in the United States. Although it is most often associated with self-limiting diarrheal disease, a small proportion of infected patients develop a more serious neuro-degenerative complication known as Guillain-Barré Syndrome. Despite many important advances in the field, still remarkably little is known about its mechanisms of pathogenicity. C. jejuni has the ability to efficiently colonize the intestine of a broad range of hosts, which allows this pathogen to gain access to the food chain thus presenting major challenges to the food industry. It has been widely observed that the attack rate of C. jejuni during well-documented point-source outbreaks or controlled human infections is under 50%, and that even under conditions of heavy exposure, only a subset of individuals developed symptomatic infections. It is well established that under physiological conditions, the resident microbiota exerts a restricting effect over bacterial enteropathogens. We therefore hypothesize that some of the documented differences in susceptibility to C. jejuni infection is due to differences in the composition of the intestinal microbiota. We intend to conduct experiments to better understand the mechanisms by which the resident intestinal microbiota restricts C. jejuni colonization. To achieve this objective we plan to leverage a germ-free chicken gut colonization model that we have recently established in our laboratory along with our long-standing expertise in the study of C. jejuni. These studies will provide the foundation for the understanding of the role of the resident microbiota in C. jejuni intestinal colonization, which may serve as the bases for the development of novel strategies to combat C. jejuni infections.

项目描述 空肠弯曲杆菌是美国腹泻的最常见原因。虽然这是最大的 通常与自限性腹泻病有关，一小部分受感染患者发展更多 严重的神经化学并发症称为Guillain-Barré综合征。尽管有很多很重要 该领域的进步，对其致病性机制知之甚少。 C. Jejuni有 能够有效地定居广泛的宿主的肠子，这使该病原体进入 对于食物链，给食品行业带来了重大挑战。已经广泛观察到 记录到充分记录的点源爆发或受控人类感染期间的空肠梭菌的攻击率不在 50％，即使在大暴露的条件下，只有一部分人出现了症状 感染。众所周知，在物理条件下，居民微生物群执行限制 对细菌肠病毒的作用。因此，我们假设某些已记录的差异 对空肠梭菌感染的敏感性是由于肠道菌群组成的差异。我们 打算进行实验，以更好地了解居民肠道菌群的机制 限制了空肠C.殖民化。为了实现这一目标，我们计划利用无菌鸡肠 我们最近在实验室中建立的殖民模型以及我们的长期专业知识 J. Jejuni的研究。这些研究将为理解居民的作用奠定基础 空肠梭状芽胞杆菌中的微生物群，它可以用作发展的基础 打击冠状动脉杆菌感染的策略。