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Drugs, Germs, and Joints: Antibiotics, Gut Microbiota, and Juvenile Idiopathic Arthritis

药物、细菌和关节：抗生素、肠道微生物群和幼年特发性关节炎

基本信息

批准号：
9164039
负责人：
Daniel Benjamin Horton
金额：
$ 18.99万
依托单位：
RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
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：
2016-09-15 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9164039
关键词：
Accounting Age Anti-Inflammatory Agents Anti-inflammatory Antibiotics Antirheumatic Agents Arthritis Autoimmune Process Autoimmunity Bioinformatics Biometry Case Series Case-Control Studies Categories Child Childhood Chronic Chronic Childhood Arthritis Chronic Disease Clinical Clinical Data Communities Complex Complication Controlled Study Data Data Collection Databases Development Diagnosis Disease Dose Drug usage Epidemiologist Epidemiology Etiology Exhibits Eye Family Feces Flare Future Genetic Predisposition to Disease Germ Goals Grant Human Human Microbiome Infection Inflammation Inflammatory Intestines Joints Lead Learning Link Longitudinal Studies Mediating Mentors Mentorship Methods Newly Diagnosed Oral Oral cavity Pathogenesis Pattern Pharmaceutical Preparations Pharmacoepidemiology Play Population Principal Investigator Process Property Proxy Psoriasis Recruitment Activity Recurrence Reporting Research Research Activity Research Design Research Personnel Rheumatism Rheumatoid Arthritis Rheumatology Risk Role Sampling Self-control as a personality trait Statistical Methods Testing Time Training Training Activity Uveitis Vision antimicrobial base biomedical informatics career development clinical phenotype cohort course development design enthesitis experience gut microbiota high risk insight microbial microbiome microbiota novel patient oriented patient oriented research prevent prospective rheumatologist sex skills species difference

项目摘要

Project Summary Little is known about why children develop juvenile idiopathic arthritis (JIA). Research implicates microbiome imbalance (dysbiosis) of the mouth and gut in the development and activity of rheumatoid arthritis, a disease distinct from most forms of JIA. Gut dysbiosis may also mediate eye inflammation (uveitis), a common, vision-threatening complication of JIA. Some children with a less common form of JIA have evidence of dysbiosis, and antibiotics (major microbiome disrupters) are associated with new-onset JIA in large populations. The overall goal of this research is to understand the mechanisms underlying the development and course of JIA in order to develop new ways of preventing and treating this family of chronic diseases. The main objective of this study is to examine the complex relationship between antibiotics, infections, and dysbiosis in relation to JIA pathogenesis and activity. This project will focus on the most common form of JIA, oligoarticular JIA, which is associated with high rates of uveitis. The first aim will examine whether gut microbiota from children with incident oligoarticular JIA exhibit dysbiosis (primary exposure) compared with gut microbiota of matched unaffected children in a multicenter case-control study of prospectively recruited children. The second aim will prospectively follow those children with oligoarticular JIA to determine whether gut dysbiosis A) resolves with inactive disease (in a self-controlled study comparing microbiota at diagnosis and at the time of inactive disease) and/or B) increases with JIA flare (in a case-control study comparing microbiota at flare and at the time of inactive disease). Both aims will use self-collected stool samples along with clinical data, including antibiotic use (secondary exposure). Dysbiosis will be defined as having decreased gut microbial diversity and distinct overall microbial composition relative to the comparator group. The analysis will also explore differences in the relative abundance of specific species between groups as well as associations between dysbiosis and clinical features of JIA (e.g., uveitis). The third aim will test whether antibiotic use in children with JIA, particularly drugs with antianaerobic coverage, is associated with new antirheumatic drug use within 3 months as a proxy for increased JIA disease activity. This aim will use administrative claims data and a self-controlled case series design. The proposed K23 project will provide this pediatric rheumatologist with an integrated plan of mentored patient-oriented research, career development activities, and formal training in bioinformatics. Guided by expert mentors and talented collaborators, the research and training activities outlined in this application will enable the principal investigator to mature from an observational epidemiologist into an independent patient- oriented and translational researcher. These opportunities will equip this investigator with a much larger set of skills to answer important and novel questions about pediatric rheumatic diseases.

项目总结