Affinity between gut microbiota and ankylosing spondylitis: insight from causal analysis

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton.
• The gut microbiota's role in AS pathogenesis is not well understood.
• Current AS pharmacotherapy is limited, especially for non-unstable cases.

Purpose of the Study:

• To investigate potential causal links between gut microbiota composition and AS susceptibility using Mendelian Randomization (MR).
• To identify specific bacterial taxa associated with increased or decreased risk of developing AS.

Main Methods:

• Utilized large-scale genome-wide association study (GWAS) datasets for gut microbiota (18,340 individuals) and AS (9,069 cases, 1,550 controls).
• Applied multiple MR methods, heterogeneity testing, and horizontal pleiotropy assessment.
• Conducted "leave-one-out" sensitivity analyses to ensure robustness of findings.

Main Results:

• Identified 10 bacterial traits significantly associated with AS risk.
• Four taxa increased AS risk: Actinobacteria, Streptococcaceae, Enterorhabdus, and Ruminococcaceae NK4A214 group.
• Six taxa decreased AS risk: Lactobacillaceae, Rikenellaceae, Anaerotruncus, Eubacterium oxidoreducens group, Howardella, and Oscillibacter.

Conclusions:

• Provides evidence for a causal relationship between specific gut bacteria and AS.
• Highlights the potential of the gut-spine axis in AS.
• Suggests microbiota-targeted interventions as a potential therapeutic strategy for ankylosing spondylitis.