Objective:

To propose a novel theoretical framework for understanding the mechanisms by which intestinal dysfunction contributes to persistent joint inflammation in gout, emphasizing the role of gut microbiota.

Key Findings:

• Gout is characterized by a systemic metabolic disorder linked to the gut-joint axis, with specific microbial changes contributing to inflammation.
• Intestinal dysbiosis, particularly the loss of butyrate-producing bacteria and the expansion of Gram-negative pathogens, is observed in gout patients, affecting inflammatory responses.
• OMVs are proposed as key mediators for delivering gut-derived inflammatory signals to joints, highlighting their role in the pathogenesis of gout.

Interpretation:

The proposed model emphasizes the need for a comprehensive understanding of the gut-joint signaling cascade in gout pathogenesis, suggesting new avenues for research.

Limitations:

• The hypothesis requires further experimental validation to establish the proposed mechanisms, particularly through mechanistic studies.
• Current literature primarily focuses on correlational analyses rather than mechanistic explanations, indicating a gap in understanding.

Conclusion:

The review aims to provide a conceptual foundation for precision medicine approaches in gout management, shifting focus from symptom relief to addressing underlying mechanisms, which is crucial for effective treatment.