Microbial ecology of the inflamed intestine

发炎肠道的微生物生态学

基本信息

批准号：
10462602
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 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10462602
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 inflammation gut microbiome gut microbiota improved in vivo 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.

项目概要沙门氏菌病是影响人类和农业的最重要的食源性疾病之一。肠道菌会引起宿主肠道炎症，从而破坏正常的沙门氏菌群。然后，沙门氏菌依靠微生物群不消耗的营养物质而茁壮成长，这些营养物质来源包括 1,2-。丙二醇，是微生物群的产物；乙醇胺，来自受损细胞；葡萄糖二酸和半乳二酸，源自Nos2介导的葡萄糖和半乳糖氧化；和源自饮食的果糖天冬酰胺 (F-Asn) F-Asn 利用系统提供了一种途径。有趣的治疗目标，因为抑制 FraB 酶会通过代谢使细菌中毒我们的主要目标是使用系统级方法来确定主要营养源。随着时间的推移，沙门氏菌在发炎的肠道中利用并识别出竞争这些微生物的微生物我们追求其中一些营养获取系统将为以下疾病提供治疗目标。沙门氏菌和潜在的其他肠杆菌科细菌，包括耐碳青霉烯类肠杆菌科细菌 (CRE) 被 CDC 报告列为“紧急”威胁，“美国的抗生素耐药性威胁” 在其他情况下，我们努力将竞争性微生物用作益生菌或益生菌。我们建议将营养素用作益生元来实现我们的目标并测试我们的假设。具有以下两个目标：1）确定沙门氏菌介导的化学和生物指标随着时间的推移，炎症；2) 描述沙门氏菌与其竞争者之间的代谢交换。这些目标的实现将极大地扩展我们对肠道微生物生态学的理解。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。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Optimization of proteomics sample preparation for identification of host and bacterial proteins in mouse feces.

DOI：
10.1007/s00216-022-03885-z
发表时间：
2022-03
期刊：
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
影响因子：
4.3
作者：
Baniasad, Maryam;Kim, Yongseok;Shaffer, Michael;Sabag-Daigle, Anice;Leleiwi, Ikaia;Daly, Rebecca A.;Ahmer, Brian M. M.;Wrighton, Kelly C.;Wysocki, Vicki H.
通讯作者：
Wysocki, Vicki H.

Exposing new taxonomic variation with inflammation - a murine model-specific genome database for gut microbiome researchers.

DOI：
10.1186/s40168-023-01529-7
发表时间：
2023-05-20
期刊：
Microbiome
影响因子：
15.5
作者：
通讯作者：

Chemical and pathogen-induced inflammation disrupt the murine intestinal microbiome.

DOI：
10.1186/s40168-017-0264-8
发表时间：
2017-04-27
期刊：
Microbiome
影响因子：
15.5
作者：
Borton MA;Sabag-Daigle A;Wu J;Solden LM;O'Banion BS;Daly RA;Wolfe RA;Gonzalez JF;Wysocki VH;Ahmer BMM;Wrighton KC
通讯作者：
Wrighton KC

DRAM for distilling microbial metabolism to automate the curation of microbiome function