Inflammation-derived sugars lower resistance against Salmonella

炎症衍生的糖会降低对沙门氏菌的抵抗力

• 批准号: 8974262
• 负责人: Andreas J Baumler
• 金额: $ 19.59万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8974262
• 关键词: Address; Animal Model; Antibiotic Therapy; Antibiotics; Biochemistry; Carbohydrates; Clostridium difficile; Communicable Diseases; Data; Development; Diarrhea; Environment; Equilibrium; Funding Mechanisms; Generations; Genes; Goals; Growth; Health; Immune response; Indigenous; Infection; Inflammation; Inflammatory Bowel Diseases; Inflammatory Response; Inflammatory disease of the intestine; Intestinal Diseases; Irritable Bowel Syndrome; Knowledge; Laboratories; Large Intestine; Measures; Modeling; Molecular; Mucous Membrane; NOS2A gene; Nitrogen; Nutrient; Nutritional; Operative Surgical Procedures; Outcome; Oxygen; Pathogenesis; Patients; Predisposition; Property; Reactive Nitrogen Species; Relapse; Research; Resistance; Salmonella; Salmonella enterica; Salmonella typhimurium; Science; Testing; Work; base; enteric pathogen; expectation; foodborne pathogen; innovation; microbial community; microbiota; novel; oxidation; pathogen; research study; sugar

 DESCRIPTION (provided by applicant): The microbial community inhabiting the large intestine confers protection against enteric pathogens, a property known as "colonization resistance". A disruption of the microbial community by antibiotic treatment is accompanied with increased susceptibility to infections with enteric pathogens, such as Salmonella enterica. However, the mechanisms lowering "colonization resistance" after antibiotic treatment remain poorly understood, which represents a key gap in knowledge that will be addressed in this application. Our central hypothesis is that antibiotic treatment induces a mild inflammatory response associated with the generation of reactive oxygen and nitrogen species, which in turn react with carbohydrates to generate inflammation-derived nutrients that fuel luminal growth of S. enterica. We will test key aspects of our hypothesis by determining whether oxidized carbohydrates reduce "colonization resistance" against S. Typhimurium after antibiotic treatment (Aim 1). It is our expectation that successful completion of the proposed experiments will establish the innovative new concept that the local inflammatory response creates a unique nutritional environment that is conducive to a bloom of enteric pathogens capable of utilizing inflammation-derived nutrients. Successful completion will be significant because results from this work will have broad relevance for understanding the mechanisms underlying "colonization resistance" against enteric pathogens, changes in microbial communities during conditions of intestinal inflammation (e.g. inflammatory bowel disease), and the pathogenesis of antibiotic-related intestinal disorders (e.g. irritable bowel syndrome).

 描述（应用程序提供）：居住在肠道病原体的大肠贡献保护的微生物群落，该物业被称为“殖民化抗性”。通过抗生素治疗对微生物群落的破坏是通过增加促进病原体（例如沙门氏菌）感染的敏感性来实现的。然而，抗生素处理后降低“定殖抗性”的机制仍然很少了解，这代表了本应用中将解决的知识的关键差距。我们的中心假设是抗生素治疗引起了与活性氧和氮的产生相关的轻度炎症反应，而活性氧和氮物种则与碳氢化物反应产生炎症衍生的营养素，从而为肠链球菌的腔内生长燃料。我们将通过确定氧化的碳液在抗生素治疗后是否降低针对伤寒链霉菌的“定殖耐药性”来检验假设的关键方面（AIM 1）。我们期望成功完成拟议的实验将建立创新的新概念，即局部炎症反应创造了一种独特的营养环境，该环境正在为能够利用感染源营养素的一批肠道病原体进行。成功完成将是重要的，因为这项工作的结果将在理解针对肠道病原体的“抗性性”，肠道感染条件下微生物群落的变化（例如炎症性肠病）以及抗生素相关的肠道疾病的发病机制（例如，抗生素疾病的发病机构（例如，抗riiltialital controperome consyme）的变化具有重要意义。