Microbial ecology of the inflamed intestine

发炎肠道的微生物生态学

基本信息

批准号：
10227082
负责人：
Brian M Ahmer
金额：
$ 70.6万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-24 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10227082
关键词：
Adult Affect Agriculture Animals Antibiotic Resistance Antibiotics Asparagine Bacteria Bacterial Infections Biological Biological Assay CBA/J Mouse Centers for Disease Control and Prevention (U.S.)Chemicals Chemistry Child Clostridium Coupled Crohn&apos s disease Data Diet Disease Disease model Ecology Ecosystem Elderly Enterobacteriaceae Environment Enzymes Ethanolamines Floods Fructose Future Galactose Genome Genomics Glucose Goals Growth Human Immunocompromised Host In Vitro Individual Infection Inflammation Inflammatory Inflammatory Bowel Diseases Intervention Intestines Knowledge Lead Mediating Metabolic Microbe Modeling Morbidity - disease rate Nutrient Oxidants Pathway interactions Physiology Predisposition Probiotics Process Propylene Glycols Reporting Research Resistance development Resolution Salmonella Salmonella enterica Salmonella infections Salmonella typhimurium Sampling Serotyping Severities Sodium Dextran Sulfate Source Structure System Technology Testing Therapeutic Time Translating Ulcerative Colitis United States Vaccines Viral Virus Diseases base carbapenem-resistant Enterobacteriaceae cell injury commensal microbes foodborne illness foodborne infection foodborne pathogen gastrointestinal infection gut microbiome gut microbiota improved in vivo inflammatory disease of the intestine metabolome metabolomics microbial microbial community microbiota microorganism interaction mortality mouse model multiple omics non-typhoidal Salmonella normal microbiota novel therapeutic intervention oxidation pathogen prebiotics prophylactic therapeutic target

项目摘要

Project Summary Salmonellosis is one of the most significant food-borne diseases affecting humans and agriculture. Salmonella enterica induces inflammation of the host intestinal tract, which disrupts the normal microbiota. Salmonella then thrives on the nutrients that are not consumed by the microbiota. Salmonella nutrient sources include 1,2- propanediol, which is a product of the microbiota; ethanolamine, which is derived from damaged cells; glucarate and galactarate which are derived from Nos2-mediated oxidation of glucose and galactose; and fructose-asparagine (F-Asn) which is derived from the diet. The F-Asn utilization system provides an interesting therapeutic target as inhibition of the FraB enzyme intoxicates the bacterium with a metabolic intermediate. Our primary objectives are to use a systems-level approach to identify the major nutrient sources utilized by Salmonella over time in the inflamed gut and to identify the microbes that compete for those nutrients. We hypothesize that some of these nutrient acquisition systems will provide therapeutic targets for Salmonella and potentially other Enterobacteriaceae, including the carbapenem-resistant Enterobacteriaceae (CRE) that are classified as an “urgent” threat by the CDC report, “Antibiotic resistance threats in the United States”. In other cases, we hypothesize that the competing microbes could be utilized as probiotics or the nutrients utilized could be utilized as prebiotics. We propose to fulfill our objectives and test our hypotheses with the following two aims: 1) Identify the chemical and biological indicators of Salmonella-mediated inflammation over time; 2) characterize metabolic exchanges between Salmonella and its competitors in the gut. The fulfillment of these aims will greatly expand our understanding of the microbial ecology of salmonellosis and may be broadly relevant to other pathogens or related inflammatory disorders.

项目摘要沙门氏菌是影响人类和农业的最重要的粮食传播疾病之一。沙门氏菌 Enterica诱导宿主肠道的炎症，这破坏了正常的菌群。沙门氏菌然后，微生物群未消耗的营养成就。沙门氏菌营养来源包括1,2-- 丙二醇，这是菌群的产物；乙醇胺是从受损细胞衍生的；谷氨酸和半乳酸酸酯源自NOS2介导的葡萄糖和半乳糖的氧化；和果糖 - 天冬酰胺（F-ASN）是从饮食中得出的。 F-ASN利用率系统提供了有趣的治疗靶标作为抑制与代谢的细菌抗蛋白毒素的抑制作用中间的。我们的主要目标是使用系统级别的方法来识别主要的营养资源随着时间的流逝，沙门氏菌在发炎的肠道中使用，并确定竞争的微生物营养。我们假设其中一些营养的获取系统将为沙门氏菌和可能的其他肠杆菌科，包括抗碳青霉烯的肠杆菌科（CRE）被CDC报告归类为“紧急”威胁，“统一的抗生素抗性威胁国家”。在其他情况下，我们假设可以将竞争的微生物用作益生菌或使用的营养物质可以用作益生元。我们建议实现我们的目标并检验我们的假设以下两个目的：1）确定沙门氏菌介导的化学和生物学指标随着时间的流逝炎症； 2）在沙门氏菌与其竞争对手之间的代谢交流表征肠。这些目标的实现将大大扩展我们对微生物生态的理解沙门氏菌病，可能与其他病原体或相关炎症性疾病广泛相关。