Investigating shared cellular pathology in the gut-joint axis

This research project was awarded the 2024 Birmingham BRC Collaboration Fund

Status: Ongoing

There is evidence that joint inflammation in inflammatory arthritis may start from mucosal surfaces like the intestine. This connection, known as the ‘gut-joint axis,’ is particularly evident in inflammatory bowel disease (IBD), where up to 40% of people also develop inflammatory arthritis. However, current treatments that address both gut and joint inflammation are limited, and the underlying mechanisms are not well understood. Understanding these shared mechanisms could help us tailor treatments more precisely and discover new therapy options.

Project aims

By bringing together rheumatologists and gastroenterologists from the NIHR Birmingham, Oxford and Great Ormond Street Hospital (GOSH) BRCs, our goal is to create a cross‑disciplinary pathway to recruit people with newly diagnosed IBD who also show signs of joint inflammation. This would allow us to build a unique cohort of patients and study how gut and joint inflammation are connected. 

To do this, we worked within an established IBD clinic that sees more than 400 new patients each year. A rheumatologist trained in musculoskeletal ultrasound joined the clinic to assess patients for inflammatory arthritis and identify joints suitable for a small, ultrasound‑guided biopsy. Patients undergoing routine endoscopic gut biopsies were also offered this minimally invasive joint biopsy. 

We developed and validated methods to safely collect, freeze, and store matched gut and joint tissue samples from the same patient. These samples are now being used for detailed analysis, including histology and advanced single‑cell and spatial transcriptomic techniques. We have successfully collected samples from both adults and children across several major hospitals, laying the groundwork for future multi‑centre studies. 

Early analysis of samples from eight patients has already revealed shared and distinct cell types and molecular pathways in gut and joint tissues. These first findings provide an important foundation for understanding the biology of the gut‑joint axis and guiding future research and treatment development.