Interactions between AHR ligands and the gut microbiota in murine arthritis

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DESCRIPTION (provided by applicant): 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.