The microbiota in axial spondyloarthritis: what have we learned from Mendelian randomisation studies?

Objectives: It has been postulated that the gut microbiota plays an important role in the pathogenesis of spondyloarthritis (SpA). However, cross-sectional studies are limited in their ability to differentiate disease-driven microbial alterations from causative changes. Mendelian randomisation (MR) studies leverage existing genetic associations to investigate causality, offering insights into microbiota-disease associations.

Methods: We conducted a systematic review of all MR studies that evaluated the relationship between the microbiota and axial SpA. Eight studies were identified and reviewed. To look for genetic associations with the microbiota, all of them used the MiBioGen microbiota genome-wide association study (GWAS), with one also using the Dutch Microbiome Project. To find associations between the human genome and disease, various data sources were used, including the published GWAS in ankylosing spondylitis (AS), FinnGen, the UK Biobank, and the Integrative Epidemiology Unit (IEU) Open GWAS project.

Results: MR findings revealed predicted increased abundances of Ruminococcaceae NK4A214 and Verrucomicrobia among others, alongside decreased abundances of Lactobacillaceae, and Rikenellaceae families, as well as the Bacteroides genus. These findings largely support the results from cross-sectional studies of the microbiota in patients with SpA. They suggest that bacteria that disrupt gut barrier function may result in an increased risk of SpA, while the opposite may be true with bacteria such as Alistipes and Bacteroides that may have a protective role.

Conclusions: These results underscore the interplay of genetics, microbiota, and disease. Further research is needed to refine these findings and optimise therapeutic approaches.