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

> **NIH NIH K23** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2020 · $154,452

## Abstract

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 lar...

## Key facts

- **NIH application ID:** 10000025
- **Project number:** 5K23AR070286-05
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Daniel Benjamin Horton
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $154,452
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000025

## Citation

> US National Institutes of Health, RePORTER application 10000025, Drugs, Germs, and Joints: Antibiotics, Gut Microbiota, and Juvenile Idiopathic Arthritis (5K23AR070286-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10000025. Licensed CC0.

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