Nisin Lantibiotic Mitigates Brain Microbiome Dysbiosis and Alzheimer’s Disease-Like Neuroinflammation (UCLA Case No. 2024-096)

Researchers led by Professor Yvonne Kapila in the UCLA School of Dentistry have developed a technology that harnesses nisin, a well-characterized probiotic lantibiotic bacteriocin, as a novel therapeutic to address brain microbiome dysbiosis and Alzheimer’s disease (AD)-like neuroinflammation driven by periodontal disease. By targeting the microbial imbalances and inflammatory pathways linking oral health to neurodegeneration, nisin offers a cutting-edge, biologically grounded approach to mitigate complex AD pathology.

INNOVATION:

• Microbiome Modulation: Nisin selectively eradicates pathogenic oral bacteria responsible for periodontal disease while preserving beneficial commensals, restoring microbial balance both in the oral cavity and brain microbiomes.
• Neuroinflammation Suppression: By reducing microbial-driven neuroinflammatory signals, including pro-inflammatory cytokines and microglial activation, nisin alleviates key contributors to AD-like neurodegenerative progression.
• Non-Antibiotic, Safe Profile: As a naturally occurring bacteriocin with probiotic attributes, nisin is distinguished by its safety, minimal systemic toxicity, and targeted antimicrobial action, avoiding broad-spectrum antibiotic drawbacks.
• Oral-Brain Axis Therapeutics: Targets the emerging, scientifically substantiated oral microbiome–brain axis, offering a novel intervention point in AD treatment beyond traditional amyloid-centric approaches.

ADVANTAGES:

• Disease-Modifying Potential: The ability to intervene in early or progressive AD by correcting microbiome dysbiosis and neuroinflammation provides an innovative avenue to slow or reverse cognitive decline.
• Complementary to Existing Therapies: Nisin can synergize with current and future AD treatments, enhancing overall disease management by addressing underlying microbial and inflammatory drivers.
• Broad Applicability: Beyond AD, this approach may benefit other neurodegenerative or neuroinflammatory disorders influenced by microbiome alterations, expanding market reach.
• Growing Demand: Rising awareness of the microbiome’s role in brain health aligns with increasing interest in probiotic and microbiome-based therapeutics, presenting a compelling commercial opportunity in the neurotherapeutics sector.

Related publications (by the inventors only):

Zhao, C., Kuraji, R., Ye, C. et al. Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer’s disease-like neuroinflammation triggered by periodontal disease. J Neuroinflammation 20, 228 (2023). https://doi.org/10.1186/s12974-023-02915-6