Spondyloarthritis (SpA) affects 0.5-2% of the population in the United States and is characterized by an asymmetric inflammatory arthritis, spondylitis, and enthesitis, with risk of extra-articular complications. The pathogenesis is unknown;however, despite recent genetic advances, there remains an important role for environmental triggers. One potential contributing factor is the intestinal microbiota, abnormalities in which are linked to inflammatory bowel disease. Another important environmental factor that is wrongly linked to animal models of arthritis but has not yet been studied in spondyloarthritis is the family of aryl hydrocarbon receptor ligands. It is our hypothess that both the enteric microbiota and AHR ligands contribute towards spondyloarthritis, and furthermore that the microbiota can attenuate the effects of the AHR ligands. The studies proposed herein will shed important light on these potential triggers. First, the investigators wil feed enteric microbiota from human subjects to a mouse model of arthritis, to determine whether the microbiota from arthritis patients is more effective at inducing arthritis. Second, the investigators will expose the same mice prenatally with multiple different AHR ligands to evaluate the effect of AHR ligand exposure on development of arthritis. The AHR studies will be repeated in the germ-free state, to evaluate whether the microbiota can modulate the effect of AHR ligand exposure.

Public Health Relevance

Little is known about environmental contributing factors to spondyloarthritis, a type of arthritis which affects up to two percent of the population. In this study, the investigators will use a mouse model of arthritis to study two potential factors: the intestinal bacteria and aryl hydrocarbon receptor ligands such as dioxin. These studies will help us better understand the causes of arthritis, which may in turn result in improved treatment options.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21ES024413-01
Application #
8765363
Study Section
Special Emphasis Panel (ZES1-JAB-J (AU))
Program Officer
Humble, Michael C
Project Start
2014-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$183,750
Indirect Cost
$58,750
Name
University of Alabama Birmingham
Department
Pediatrics
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294