Age- and region-specific gut microbiota dysbiosis in axial spondyloarthritis: a systematic review and meta-analysis

Background Axial spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the spine and sacroiliac joints. Emerging evidence suggests that the gut microbiota may contribute to its pathogenesis, but findings on microbial diversity and composition remain inconsistent. Methods We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library to identify studies comparing the gut microbiota between adults with axSpA and healthy controls. α-Diversity (Observed richness, Shannon, Simpson, Chao1, ACE) and microbial composition at the phylum level were extracted. Random-effects meta-analyses were performed using standardized mean differences (SMDs), with subgroup analyses and robustness checks (prespecified sensitivity and leave-one-out analyses). Results Twenty-five studies (n = 1639) were included. Compared with controls, axSpA was associated with lower α-diversity for Observed richness (SMD = −0.59, P = 0.04), Shannon (SMD = −0.19, P = 0.03), and Chao1 (SMD = −0.51, P = 0.02), while Simpson (SMD = −0.23, P = 0.12) and ACE (SMD = 0.42, P = 0.14) showed no significant differences. In age-stratified analyses, reductions were more apparent in participants >40 years (Shannon: SMD = −0.38, P = 0.002; Simpson: SMD = −0.50, P = 0.001). Sensitivity and leave-one-out analyses were directionally consistent; however, observed richness and Shannon became non-significant after excluding non-comparable datasets. Phylum-level findings were summarized descriptively, suggesting lower Bacteroidota and Actinobacteriota and higher Proteobacteria in axSpA. Conclusion axSpA is associated with reduced α-diversity and compositional shifts in gut microbiota, but the magnitude of effects varies across studies. Heterogeneity and methodological differences warrant cautious interpretation. Longitudinal and functional studies are needed to clarify causality and therapeutic implications. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251089098.