The role of the microbiome in rheumatoid arthritis

Abstract

The human microbiome plays a vital role in both health and disease. The evolution of molecular techniques to characterise entire microbiome communities has renewed interest in the involvement of microorganisms in the pathogenesis of Rheumatoid arthritis (RA). In this thesis, 16S and ITS amplicon sequencing were used to characterise bacterial and fungal DNA present in a range of human and mouse samples. Firstly, characterisation of the microbiome present in blood samples obtained from human RA, ankylosing spondylitis, and psoriatic arthritis patients was carried out, relative to healthy controls. Results revealed that the bacterial population in the serum of RA patients was distinct from the healthy state. Through the analysis of paired RA patient blood taken before and three months after treatment, partial microbiome normalisation was identified and was particularly evident in seronegative arthritis patients. Next, the presence and identity of bacterial and fungal communities were investigated in samples of synovial fluid obtained from human RA patients and healthy controls. Our findings revealed that the synovial fluid microbiome of RA could be distinguished from control.
Further, IL6, IL71A, IL22, IL23 were elevated in the blood and synovial fluid of RA subjects. The association of IL6 with bacteria and fungi microbiome was observed in the RA synovial fluid. Finally, a characterisation of the bacterial community members presents in the stool, urine, synovial fluid, blood, and serum from collagen-induced arthritis (CIA) and control mouse samples were undertaken. Here, we demonstrated that the bacterial community in CIA stool samples was distinct from the control.
These data propose that the human blood and synovial fluid microbiome and gut microbiome of the mice is modulated by disease status (RA) and therefore have the potential to serve as a novel biomarker in RA pathogenesis and treatment response. Further, studies are required to investigate these initial findings.