Metagenomic Analysis Reveals a Mitigating Role for Lactobacillus paracasei and Bifidobacterium animalis in Experimental Periodontitis

Probiotics have aroused increasing concern as an intervention strategy for periodontitis (PD), but their underlying mechanism of action remains poorly characterized. Regarding the significance of oral microbiota dysbiosis related to PD, we predicted that the preventive activity of probiotics may be influenced by suppressing the bacterial pathogenicity. Herein, we investigated the effects of Lactobacillus paracasei L9 (L9) and Bifidobacterium animalis A6 (A6) on PD using a rat model, and demonstrated a regulatory effect of probiotics on oral flora from a metagenomics perspective. Oral administration of A6 or L9 effectively relieved gingival bleeding, periodontal inflammatory infiltration, and alveolar bone resorption. In addition, A6 or L9 treatment reduced the inflammatory response and increased the expression of anti-inflammatory cytokines, which we expected to ameliorate alveolar bone resorption as mediated by the receptor activator of the nuclear factor-κB ligand/OPG signaling pathway. More importantly, using metagenomic sequencing, we showed that probiotics significantly altered the taxonomic composition of the subgingival microbiome, and reduced the relative proportions of pathogenic bacterial genera such as Streptococcus, Fusobacterium, Veillonella, and Escherichia. Both probiotics significantly inhibited levels of bacterial virulence factors related to adherence, invasion, exoenzyme, and complement protease functions that are strongly correlated with the pathogenesis of PD. Our overall results suggest that A6 and L9 may constitute promising prophylactic agents for PD, and should thus be further explored in the future.