Decoding Antibiotic-induced Susceptibility to Clostridium difficile Infection

解读抗生素诱导的艰难梭菌感染易感性

基本信息

批准号：
9108593
负责人：
ROBERT A BRITTON
金额：
$ 150万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-20 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9108593
关键词：
Address Adopted Adult Affect Algorithms Antibiotic Resistance Antibiotic Therapy Antibiotics Antibodies Antibody Response Antitoxins Appearance Autistic Disorder Bacterial Drug Resistance Bile Acids Biochemical Pathway Bioinformatics Bioreactors Butyric Acids Child Childhood Clinical Clostridium difficile Communities Community Networks Consumption Control Groups Coupled Coupling DNA Data Data Set Dependency Development Diarrhea Diet Digestive System Disorders Disaccharides Disease Disease Progression Drug resistance Ecosystem Epidemic Epidemiology Etiology Evaluation Feces GABA Agonists Germination Goals Health Services Heme Hospitals Human Human Microbiome Immunity Infection Inflammatory disease of the intestine Intestinal Diseases Intestines Life Link Logistic Regressions Mass Spectrum Analysis Measures Metabolic Metabolic Pathway Metadata Metagenomics Metronidazole Metronidazole resistance MicroRNAs Microbe Modeling Molecular Nosocomial Infections Outcome Outcome Measure Pathogenesis Patient risk Patients Population Predisposition Prospective Studies Publishing Recurrence Refractory Relapse Reproduction spores Research Research Personnel Resistance Resistance profile Resolution Resources Ribotypes Risk Risk Factors Role Shotguns Signal Transduction Staging Structure Systems Biology Technology Testing Texas Treatment Failure Treatment outcome Trehalose Virulence Work antimicrobial base clinical phenotype clinical risk cohort enteric pathogen experience gamma-Aminobutyric Acid gulf coast gut microbiome gut microbiota high risk in vivo innovation insight metabolomics methicillin resistant Staphylococcus aureus microbial microbial community microbiome microbiota novel diagnostics novel therapeutics outcome forecast pathogen patient registry primary outcome profiles in patients public health relevance secondary outcome temporal measurement trait whole genome zolpidem

项目摘要

DESCRIPTION (provided by applicant): The Human Microbiome Project (HMP) consortium established a unique population-scale framework which characterized the relationship between the human host and its microbial communities. These data provide strong initial evidence for host influences on microbial community structure and underscores the capacity for metagenomics and metabolomics to explore host-pathogen interactions in disease states. We will adopt such a systems biology approach to extend our published and preliminary findings as they relate to Clostridium difficile infection (CDI), antibiotic resistance and treatment outcome i children and adults. By comparisons with our pediatric and adult HMP reference datasets, we provide much needed insight into how antibiotics affect intestinal ecosystems over multiple life stages. Because young children are generally asymptomatic carriers of C. difficile whereas adults often become symptomatically infected, our proposed studies provide a developmental perspective of intestinal ecosystems that modulate C. difficile virulence and drug resistance. The novelty of our work is our discovery of an intestinal ecosystem that is refractory to frontline antibiotic therapy, the result of which is treatment failure in CDI patients. Our project goal is t identify microbes that regulate host susceptibility to C. difficile through characterization of newy-identified molecular and biochemical pathways. The combination of cutting edge multi-omics, coupled with real-time measurement of antibiotic resistance and clinical phenotyping in patients is expected to generate a valuable resource that provides new discovery into host susceptibility to CDI. To achieve these objectives we will pursue two aims: Aim 1: Unbiased longitudinal multi-omic studies of host-microbe interactions in CDI development. Aim 2: Targeted mechanistic studies of host-microbe interactions that affect treatment outcome in CDI. Through these longitudinal multi-omics studies, we expect to define host-microbe interactions that are predictive of antibiotic treatment failure in CDI patients and provide a rich array of resources - supported in part by our own ongoing CDI patient registry, the Texas Department of State Health Services, Autism Speaks, the TMC Digestive Disease Center and integrated microbiome centers (Center for Metagenomics and Microbiome Research (CCMR) and Texas Children's Microbiome Center (TCMC)).

描述（由申请人提供）：人类的微生物组项目（HMP）建立了一个独特的人口规模的框架，这些框架是人类宿主ATS微生物群落提供的强大初步证据。为了使我们发表在疾病状态的遗传和代谢组中，我们已发表的宿主病态是与我们的儿童和成人相比，我们的初步发现与梭子裂（CDI）相关。阶段。抗生素治疗是CDI患者的治疗失败，通过对生化途径的新识别来表征抗生素的抗生素耐药性。发现宿主对CDI的敏感性。通过这些纵向多词的研究，我们希望定义CDI患者抗生素治疗失败的宿主 - 微生物相互作用，并提供了丰富的资源 - 我们自己正在进行的CDI患者Regis试验Speaks，TMC消化疾病中心和综合微波经中心（宏基因组学和微生物组研究中心）和德克萨斯州儿童微生物组中心（TCMC）。