The gut-joint axis in gout: microbial outer membrane vesicles and m6A-mediated metabolic-epigenetic coupling from acute flare to chronicity

By
Yiyang Qi
Jixiang Bai
Dewei Liu
Shuhui Wang
June 8, 2026
0 min

Frontiers In Immunology

Overview

This review presents a novel framework for understanding gout as a systemic metabolic disorder influenced by the gut-joint axis. It highlights the role of bacterial outer membrane vesicles and m6A epigenetic modifications in the transition from acute gout flares to chronic inflammation.

Background

Gout is increasingly recognized as a complex metabolic autoinflammatory disease rather than a localized joint condition. The rising prevalence of gout, particularly among younger populations, underscores the need for a deeper understanding of its pathophysiology. Investigating the gut-joint connection may reveal new therapeutic targets for managing this challenging condition.

Data Highlights

No numerical data or trial data presented in the article.

Key Findings

The gut-joint axis plays a crucial role in the pathogenesis of gout.
Bacterial outer membrane vesicles (OMVs) are implicated in delivering inflammatory signals from the gut to the joints.
m6A epigenetic modifications contribute to the pro-inflammatory memory in synovial macrophages.
Intestinal dysbiosis, characterized by a loss of microbial diversity, is associated with gout onset.
Emerging therapeutic strategies include targeting OMV release and m6A enzymes to mitigate inflammation.

Clinical Implications

Understanding the gut-joint connection may shift gout management towards more precise interventions targeting the underlying mechanisms of inflammation. Clinicians should consider the role of gut health in the treatment and prevention of gout flares.

Conclusion

The proposed framework for gout emphasizes the importance of inter-organ communication and epigenetic factors in disease progression. Future research is needed to validate these concepts and explore new therapeutic avenues.