The potential role of the gut microbiota in the development of autoantibodies associated with Spondyloarthritis: a narrative review

Spondyloarthritis (SpA) is a set of immune-inflammatory conditions characterized by musculoskeletal and extra-articular manifestations. Increasing evidence indicates that alterations in the gut microbiota (dysbiosis) may influence both mucosal and systemic immune responses, potentially contributing to the loss of tolerance and the development of autoantibodies in SpA. This narrative review examines the current evidence linking gut dysbiosis to autoantibody development in SpA, with particular focus on ankylosing spondylitis (AS) and psoriatic arthritis (PsA). We summarized key mechanistic pathways, including Th17 axis activation, molecular mimicry, increased intestinal permeability (“leaky gut”), and altered microbial metabolite signaling. We discussed the potential relevance of these mechanisms to SpA-associated autoantibodies such as anti-CD74, anti-HSP65, and anti-Kaiso. Where direct evidence in SpA is limited, findings from other autoimmune diseases are considered as mechanistic analogies rather than definitive parallels. We further review microbiome-targeted therapeutic strategies, including probiotics, prebiotics, and bacterially based therapies, and highlight differences between preclinical findings and available clinical data. Although biologically plausible mechanisms, direct causal evidence linking gut dysbiosis to autoantibody production in SpA remains limited, and clear methodological heterogeneity persists across microbiome studies. Overall, while modulation of the gut-immune axis represents a promising research direction in SpA, further mechanistic and longitudinal human studies are required before microbiota-targeted interventions can be considered applicable for autoantibody modulation. The graphical abstract illustrates the role of gut microbiota in SpA (a), highlighting how gut dysbiosis (b) contributes to immune dysregulation and the development of autoantibodies such as anti-CD74, anti-HSP65, and anti-Kaiso (c,d). Dysbiosis may influence immune responses through mechanisms including T-cell activation, molecular mimicry, and increased intestinal permeability, ultimately contributing to systemic inflammation. The graphical abstract also highlights the association with HLA-B27 and illustrates how microbial imbalance may contribute to axial and peripheral manifestations of SpA. Furthermore, it presents therapeutic approaches targeting gut dysbiosis, including probiotics, bacteriotherapy, and prebiotics (e), while highlighting current challenges and limitations in microbiome research and therapy development. Understanding the gut–immune axis is important for advancing future treatment strategies in SpA.