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 空肠弯曲菌是美国食源性腹泻的最常见原因。虽然这是最 通常与自限性腹泻病相关，一小部分感染患者会出现更多症状 严重的神经退行性并发症，称为吉兰-巴利综合征。尽管有许多重要的 尽管该领域取得了进展，但对其致病机制仍知之甚少。空肠弯曲菌具有 能够有效地定植于多种宿主的肠道，从而使该病原体能够进入 食品链因此给食品工业带来了重大挑战。人们广泛观察到， 在有据可查的点源暴发或受控人类感染期间，空肠弯曲菌的发病率低于 50%，即使在严重暴露的情况下，也只有一小部分人出现症状 感染。众所周知，在生理条件下，常驻微生物群会发挥限制作用 对细菌性肠道病原体的作用。因此，我们假设一些记录在案的差异 对空肠弯曲菌感染的易感性是由于肠道微生物群组成的差异造成的。我们 打算进行实验以更好地了解常驻肠道微生物群的机制 限制空肠弯曲菌定殖。为了实现这一目标，我们计划利用无菌鸡肠 我们最近在实验室建立的殖民模型以及我们长期的专业知识 空肠弯曲菌的研究。这些研究将为理解居民的角色奠定基础 空肠弯曲菌肠道定植的微生物群，这可能作为开发新的基础 对抗空肠弯曲菌感染的策略。