NDORMS DPhil & MSc by Research
The role of the gut microbiome in tendinopathy and OA
OUTLINE OF RESEARCH PROPOSAL
The gastrointestinal (GI) tract is home to a community of microorganisms that comprise the microbiome. This microbiome varies between individuals and in health and disease. It has long been evidenced that the composition of the gut microbiome can influence pathogenesis of inflammatory diseases of the GI tract.
The GI microbiome can also alter epithelial and mucosal permeability allowing immune cells and microbiome-associated proteins to enter the circulation and impact distal systems. The classic inflammatory musculoskeletal disorders Rheumatoid Arthritis and Ankylosing Spondylitis have recently been linked to dysregulation of the GI microbiome.
Tendinopathy and OA are common musculoskeletal disorders that both have a distinct and inherent inflammatory component to their initiation and progression. Degradation and structural changes to tendon and cartilage typify tendinopathy and OA respectively. Enthesopathy, whereby inflammation and structural changes occur at tendon and ligament insertion sites, is also common in both tendinopathy and OA.
The association between the microbiome and these disorders has not been well studied. However dysregulation of regulatory T cell levels of patients with OA and alterations in the immune cell and cytokine profiles of those with both diseases strongly suggest an important influence of the microbiome on pathogenesis.
The aim of this work is to characterize the gut microbiome and its relationship to soft tissue biology in healthy control, tendinopathic and OA patients. We hypothesise that the GI microbiome will differ between controls and different disease statuses. We propose that this difference in microbiome populations will regulate the inflammatory activity of joint-resident cells. Ultimately this work will allow us to establish whether the microbiome signature can be used as a surrogate to assess disease status and whether its manipulation through diet and probiotics is a potential treatment in OA and tendinopathy.
- Use 16S rRNA profiling on fecal samples to provide a signature of the microbiome in controls and patiens with defined stages of tendinopathy and OA.
- Measure fecal markers of instestinal inflammation (e.g. calprotectin) in controls, and patients with defined stages of tendinopathy and OA.
- Measure expression and levels of disease-stage specific microbiome-relevant cytokines in tendinopathic, OA and control joint tissues.
- Assess the impact of these microbiome-relevant fatty acids and cytokines on tendon and cartilage cell activity.
- Survey established cohorts of patients with enthesopathy (tendon and cartilage) to determine the prevalence of inflammatory bowel disease and to explore the possibility of the gut microbiome being a trigger for enthesopathy.