Microbial ecology of the inflamed intestine

发炎肠道的微生物生态学

• 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
• 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' 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

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 沙门氏菌病是影响人类和农业的最重要的食源性疾病之一。沙门 肠毒素引起宿主肠道的炎症，这破坏了正常的微生物群。沙门 然后靠微生物群不消耗的营养物质繁衍。沙门氏菌的营养来源包括1，2- 乙醇胺，其来源于受损细胞; 葡糖二酸和半乳糖二酸，其衍生自Nos 2介导的葡萄糖和半乳糖的氧化;和 果糖-天冬酰胺（F-Asn），来源于饮食。F-Asn利用系统提供了 有趣的治疗靶点，因为FraB酶的抑制会使细菌因代谢而中毒 中间体我们的主要目标是使用系统级方法来识别主要营养源 随着时间的推移，沙门氏菌在发炎的肠道中利用这些细菌，并确定竞争这些细菌的微生物。 营养素我们假设其中一些营养获取系统将为以下患者提供治疗靶点 沙门氏菌和潜在的其他肠杆菌科，包括碳青霉烯类耐药肠杆菌科 (CRE)疾病预防控制中心的报告“美国的抗生素耐药性威胁”将其列为“紧急”威胁。 国家”。在其他情况下，我们假设竞争的微生物可以被用作益生菌或益生菌。 所利用的营养物可用作益生元。我们建议实现我们的目标，并测试我们的假设 主要有两个目的：1）确定沙门氏菌介导的化学和生物学指标 随着时间的推移炎症; 2）表征沙门氏菌及其竞争对手之间的代谢交换， 直觉这些目标的实现将大大扩展我们对微生物生态学的理解。 沙门氏菌病，并可能广泛相关的其他病原体或相关的炎症性疾病。

项目成果

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

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

• DOI: 10.1093/nar/gkaa621
• 发表时间: 2020-09-18
• 期刊: NUCLEIC ACIDS RESEARCH
• 影响因子: 14.9
• 作者: Shaffer, Michael;Borton, Mikayla A.;Wrighton, Kelly C.
• 通讯作者: Wrighton, Kelly C.

CAMPER: curated annotations for profiling microbial polyphenol metabolic potential.

CAMPER：用于分析微生物多酚代谢潜力的精选注释。

• DOI: 10.1101/2023.09.24.559193
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: McGivern,BridgetB;Woyda,Reed;Flynn,RoryM;Wrighton,KellyC
• 通讯作者: Wrighton,KellyC