Nisin Probiotic Prevents Periodontal Disease and Inflammation while Promoting Periodontal Regeneration and a Shift Toward a Healthy Microbiome/Virome

Abstract

\n BackgroundDysbiosis of the oral microbiome mediates chronic periodontal disease, including its characteristic bone loss and host inflammatory response. Realignment of this microbial dysbiosis towards health may prevent disease. Treatment with antibiotics and probiotics can modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. Antibacterial peptides or bacteriocins, such as nisin, and nisin-producing probiotics, Lactococcus lactis, have not been examined in this context, yet warrant further examination because of their biomedical benefits in eradicating biofilms and oral pathogenic bacteria, and modulation of immune mechanisms. The goal of this study was to examine the potential for nisin and a nisin-producing probiotic to abrogate periodontal bone loss and related inflammatory landscape while modulating the composition of the oral microbiome. ResultsA polymicrobial mouse model of periodontal disease was employed for this purpose. In a disease context, nisin and the nisin-producing Lactococcus lactis probiotic significantly decreased the levels of periodontal pathogens, alveolar bone loss, oral inflammatory host response, and host-antibody response to these pathogens. Surprisingly, nisin and/or the nisin-producing L. lactis probiotic also enhanced the number of gingival fibroblasts, periodontal ligament cells, and bone lining cells in response to the polymicrobial infection. Nisin and probiotic treatment significantly shifted the oral bacteriome and virome towards the healthy control state. This shift was characterized by a unique signature; health was associated with a Proteobacteria (Marinobacter sp. B9-2), whereas 3 retroviruses (Golden Hamster Intracisternal A-particle H18, Bat gammaretrovirus, and Porcine type C oncovirus) were associated with disease. Specific disease-associated microbial species were highly correlated with IL-6 levels. ConclusionsNisin’s ability to shift the oral microbiome towards health, mitigate oral disease and the host immune response, and promote a novel regenerative periodontal phenotype, addresses key aspects of the pathogenesis of the disease. These benefits may negate the systemic effects associated with periodontal disease and reveal a new biomedical application for nisin in regenerative medicine.