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

## TL;DR

This study finds that axial spondyloarthritis is linked to changes in gut microbiota diversity and composition, with age affecting these patterns.

## Contribution

The paper provides a systematic review and meta-analysis of gut microbiota differences in axial spondyloarthritis patients compared to healthy controls.

## Key findings

- AxSpA is associated with reduced alpha diversity in gut microbiota, particularly in those over 40 years old.
- Phylum-level analysis suggests lower Bacteroidota and Actinobacteriota and higher Proteobacteria in AxSpA patients.
- Results show heterogeneity across studies, highlighting the need for longitudinal and functional research.

## Abstract

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.

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).

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.

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.

https://www.crd.york.ac.uk/prospero/, identifier CRD420251089098.