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.