Abstract This preprint presents a computational falsification and extension of the clinical findings reported by Isomura et al. (2023) regarding the link between nocturnal oral hygiene and cardiovascular disease (CVD). While observational data confirms that skipping nighttime brushing increases CVD risk, the prevailing "hygiene hypothesis"—which attributes protection solely to the removal of periodontal pathogens (Porphyromonas gingivalis) —remains mechanistically incomplete. Methodology We utilized a custom biological implementation of the Mamba State-Space Architecture (Gu & Dao, 2023) to construct a high-fidelity Digital Twin of the oral-systemic interface. This continuous-time simulation (-evolution) modeled the metabolic flux of the oral microbiome during the 8-hour sleep cycle, specifically analyzing the Enterosalivary Nitrate-Nitrite-Nitric Oxide (NO) Pathway. Key Findings Pathogenic Validation: The simulation confirms that salivary stasis during sleep facilitates bacteremia and endothelial dysfunction if biofilm is left undisturbed. Sterility Falsification: Crucially, the model demonstrates that indiscriminate sterilization (e. g. , via antiseptic mouthwash) destroys the commensal nitrate-reducing flora (Veillonella, Neisseria). Mechanism of Action: The destruction of these commensal bacteria results in a >90% reduction in nocturnal Nitric Oxide production, leading to unmediated nocturnal hypertension. Conclusion We propose the "Bio-Active Night Shield" (BANS) hypothesis: Cardiovascular protection is achieved not by a "sterile mouth, " but by a specific ecological state that combines mechanical pathogen disruption with the preservation of nitrate-reducing capability. This paper advocates for a shift from antimicrobial eradication to Microbiome Stewardship in preventive cardiology. relatedᵢdentifiers: Supplement to: 10. 1038/s41598-023-37738-1 (Isomura et al. , 2023) Keywords: Oral-Systemic Axis, Nitric Oxide, Mamba Architecture, Cardiovascular Simulation, Digital Twin, Porphyromonas gingivalis, Microbiome Stewardship, Hypertension, In Silico Medicine.
Tshibangu Kabanga (Wed,) studied this question.