Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer's disease-like neuroinflammation triggered by periodontal disease

IntroductionPeriodontitis-related oral microbial dysbiosis is thought to contribute to Alzheimer's disease (AD) neuroinflammation and brain amyloid production. Since probiotics can modulate periodontitis/oral dysbiosis, this study examined the effects of a probiotic/lantibiotic, nisin, in modulating brain pathology triggered by periodontitis.MethodsA polymicrobial mouse model of periodontal disease was used to evaluate the effects of this disease on brain microbiome dysbiosis, neuroinflammation, Alzheimer's-related changes, and nisin's therapeutic potential in this context.Results16S sequencing and real-time PCR data revealed that Nisin treatment mitigated the changes in the brain microbiome composition, diversity, and community structure, and reduced the levels of periodontal pathogen DNA in the brain induced by periodontal disease. Nisin treatment significantly decreased the mRNA expression of pro-inflammatory cytokines (Interleukin-1 beta/IL-1 beta, Interleukin 6/IL-6, and Tumor Necrosis Factor alpha/TNF-alpha) in the brain that were elevated by periodontal infection. In addition, the concentrations of amyloid-beta 42 (A beta 42), total Tau, and Tau (pS199) (445.69 +/- 120.03, 1420.85 +/- 331.40, 137.20 +/- 36.01) were significantly higher in the infection group compared to the control group (193.01 +/- 31.82, 384.27 +/- 363.93, 6.09 +/- 10.85), respectively. Nisin treatment markedly reduced the A beta 42 (261.80 +/- 52.50), total Tau (865.37 +/- 304.93), and phosphorylated Tau (82.53 +/- 15.77) deposition in the brain of the infection group.DiscussionNisin abrogation of brain microbiome dysbiosis induces beneficial effects on AD-like pathogenic changes and neuroinflammation, and thereby may serve as a potential therapeutic for periodontal-dysbiosis-related AD.

Automated summary

This study found that nisin treatment can alleviate the effects of periodontitis on brain microbiome composition, diversity, and community structure, as well as reduce the levels of periodontal pathogen DNA in the brain. It also significantly decreases the mRNA expression of pro-inflammatory cytokines in the brain and reduces the deposition of amyloid-beta and Tau proteins.