Abstract This preprint presents a computational simulation and mechanistic extension of the clinical findings reported by Isomura et al. (2025) regarding the oral-systemic etiology of Multiple Sclerosis (MS). While recent metabolomic profiling has confirmed a distinct oral dysbiosis in MS patients—characterized by the depletion of Streptococcus and proliferation of Porphyromonas gingivalis—the precise molecular pathway linking this dysbiosis to Central Nervous System (CNS) demyelination has remained elusive. Methodology We utilized the Mamba State-Space Architecture, a continuous-time biological simulation engine (-evolution), to construct a high-fidelity Digital Twin of the Oral-Vascular-Neural Axis. The simulation modeled enzymatic kinetics, metabolic flux, and blood-brain barrier (BBB) integrity over an 8-hour sleep cycle. Key Findings: The Dual-Vector Hypothesis The simulation identifies a synergistic "Dual-Vector" pathology that drives MS progression: Vector 1: The Shield Collapse (Metabolic). The depletion of commensal Streptococcus species creates a systemic "Hypotaurine Void. " Our model demonstrates that hypotaurine is essential for inhibiting lipid peroxidation in endothelial membranes. Its absence triggers localized ferroptosis in the BBB, mechanically disrupting Claudin-5 tight junctions and increasing permeability. Vector 2: The Trojan Horse (Immunogenic). The pathogen P. gingivalis expresses the enzyme Peptidylarginine Deiminase (PPAD). The simulation reveals that PPAD preferentially citrullinates C-terminal arginine residues on host proteins, creating "Neo-Epitopes" that bypass central tolerance. These modified antigens trigger high-affinity autoantibodies (ACPAs) that cross-react with Citrullinated Myelin Basic Protein (MBP) in the CNS via molecular mimicry. Conclusion We propose that MS pathogenesis is driven by an "Oral Auto-Immune Bootcamp. " The oral cavity acts as a bio-reactor where the immune system is trained to attack myelin, facilitated by a metabolically compromised BBB. Clinical management should consider the "Gingivalis/Streptococcus Ratio" and "Salivary Hypotaurine Index" as predictive biomarkers. relatedᵢdentifiers: Supplement to: 10. 1038/s41522-025-00787-7 (Isomura et al. , 2025) Keywords: Multiple Sclerosis, Porphyromonas gingivalis, Citrullination, Hypotaurine, Ferroptosis, Blood-Brain Barrier, Digital Twin, Mamba Architecture, Autoimmunity, Molecular Mimicry.
Tshibangu Kabanga (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: