The involvement of Anaeroplasma, caproic acid, and interleukins through the brain-gut axis may contribute to IgAV with neurological involvement.

BACKGROUND

Immunoglobulin A vasculitis (IgAV), the most prevalent pediatric systemic vasculitis, may involve central nervous system (CNS) manifestations with unknown mechanisms.

METHODS

To investigate gut-brain axis interactions, human gut microbiota from IgAV with or without neurological involvement and healthy children were transplanted into specific pathogen-free mice. The recipients' microbiota, fecal short-chain fatty acids (SCFAs), and serum cytokines were analyzed alongside electroencephalogram (EEG) monitoring.

RESULTS

Spike waves emerged exclusively in the EEGs of mice receiving transplants from neurologically affected IgAV children. Comparative analyses demonstrated: enrichment of Anaeroplasma in the IgAV with neurological involvement (IgAVNI) group compared to IgAV controls (P < 0.05); elevated caproic acid in IgAVNI versus controls (P < 0.05); reduced IL-1α in IgAVNI versus controls (P < 0.05); and a positive correlation between Anaeroplasma and IL-17A (r = 0.94, P = 0.004).

CONCLUSION

Gut microbiota, notably Anaeroplasma, may trigger IgAV-related CNS involvement via the gut-brain axis, co-mediated through regulation of caproic acid, IL-1α, and IL-17A.

IMPACT: First evidence that Anaeroplasma drives IgAV CNS manifestations via the gut-brain axis by regulating caproic acid, IL-1α, and IL-17A, with EEG spike waves as a specific marker. The Anaeroplasma-caproic acid-IL-17A axis fills a mechanistic gap in IgAV neurological complications, transcending current immunoinflammatory paradigms. Provides combined EEG/microbiota/metabolite biomarkers for early prediction and suggests Anaeroplasma, IL-17A, and caproic acid may represent therapeutic targets for neuroprotective interventions.