Inflammation-derived sugars lower resistance against Salmonella

 描述（由申请方提供）：栖息在大肠中的微生物群落可提供针对肠道病原体的保护，这种特性称为“定植抗性”。抗生素治疗对微生物群落的破坏伴随着对肠道病原体（如肠道沙门氏菌）感染的易感性增加。然而，抗生素治疗后降低“定植抗性”的机制仍然知之甚少，这代表了本申请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诱导与活性氧和氮物质的产生相关的轻度炎症反应，活性氧和氮物质又与碳水化合物反应产生炎症衍生的营养物质，这些营养物质为S.肠我们将通过确定氧化碳水化合物是否降低对沙门氏菌的“定植抗性”来检验我们假设的关键方面。抗生素治疗后的鼠伤寒（目的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个独特的营养环境，有利于肠道病原体的大量繁殖，能够利用炎症衍生的营养物质。成功完成将是重要的，因为这项工作的结果将有广泛的相关性，了解机制的“殖民抵抗”对肠道病原体，在肠道炎症（如炎症性肠病）的条件下，微生物群落的变化，和发病机制的过敏相关的肠道疾病（如肠易激综合征）。

 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).