Inflammatory arthritis and monogenic diseases

Overview

Inflammatory arthritis is encompassed by a wide range of multifaceted arthropathies, including Spondyloarthritis (SpA) and Reactive Arthritis. There is a clear gut component in inflammatory arthritis. Patients with SpA commonly present with intestinal inflammation, and some gut microbiota shifts are common between patients with SpA and patients with inflammatory bowel disease.

Inflammatory arthritis and other inflammatory diseases at barrier sites can be caused by a genetic mutation in one specific gene. Such diseases are also associated with alterations in the microbiome within the gut and at other sites including the lung.

The Powrie lab aims to identify and characterise the host-microbiota interactions driving systemic inflammation in arthritis and monogenic diseases using well established experimental models as well as new models that probe causal relationships between the gut microbiome and inflammation at other sites. This work aims to further our understanding of the role of the intestinal microbiota in systemic disease, and hopes to inform microbiota-based therapeutic strategies for inflammatory diseases.

Current projects

1. Exploring the role of the microbiome in reactive arthritis disease pathogenesis

Reactive Arthritis (ReA) is a form of Spondyloarthritis associated with gastrointestinal infection by enteric pathogens. The host-microbiota mechanisms driving this pathology are yet to be characterised. We are using experimental models with reduced microbiome complexity to probe pathogen and host-microbiome interactions that drive systemic inflammation in ReA. Quantification of immunoglobulin-coated bacteria and localisation of the intestinal microbiota allows us to identify bacteria with pathogenic potential, to inform the composition of microbial consortia to manipulate disease severity.

2. Understanding the role of the microbiome in monogenic diseases

Single genetic mutations in important genes can lead to early onset inflammation in the gut (inflammatory bowel disease) or lungs (cystic fibrosis). In the absence of microbes such inflammation is often reduced, suggesting a role for the microbiome in driving disease. We are using experimental models with reduced microbiome complexity to probe pathogen and host-microbiome interactions that drive systemic inflammation in models of monogenic disease.

3. The Inflammatory Athritis Microbiome Consortium (IAMC)

Professor Powrie led an international consortium of investigators that aimed to identify microbes that contribute to inflammatory arthritis. More information can be found via this link.