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The use of postbiotics, including bioactive metabolites and inactivated microbial components, is emerging as a promising novel treatment and adjuvant therapy for periodontal disease, which is characterized by chronic inflammation and alveolar bone loss.

This study evaluated the synergistic potential of a postbiotic complex consisting of heat-treated L. lactis HY449 and S. thermophilus HY9012 on gingival protection and the prevention of bone loss in cell and mouse models of periodontitis.

The results demonstrated the following functional properties of the **postbiotic complex (HY449 + HY9012)**:

• Anti-inflammatory and macrophage immunomodulation: Favorably modulated the immune response by inhibiting the production of M1 inflammatory macrophages induced by periodontal pathogen toxins while promoting the production of M2 anti-inflammatory macrophages that attenuate inflammation (cell study)
• Inhibition of osteoclast (bone-resorbing cell) differentiation: Inhibited the differentiation of osteoclasts, which are responsible for alveolar bone destruction, and potently suppressed the expression of key osteoclastogenic genes and transcription factors (cell study).
• Prevention of alveolar (gum) bone loss: Co-administration of the two strains in a mouse model of induced periodontitis demonstrated a synergistic effect in significantly attenuating alveolar bone loss (animal study).

Analyses based on cell and animal models demonstrated that the HY449 and HY9012 postbiotic complex is a highly effective synergistic agent for periodontitis management through the inhibition of oral inflammation and prevention of alveolar bone destruction.

For probiotics to be effective against oral diseases, beneficial bacteria must stably colonize the disease site to exert antibacterial and anti-inflammatory effects.

In this study, we analyzed the beneficial effects of L. lactis and S. thermophilus, both of which are well-established probiotics widely used in dairy fermentation, in a model of periodontitis caused by disruption of oral microbial homeostasis.

The results demonstrated the following functional properties of the **oral-targeted probiotics (L. lactis + S. thermophilus):

• Restoration of oral microbial homeostasis: Contributed to reestablishing the ecological balance of oral biofilms disrupted by the overgrowth of anaerobic bacteria associated with periodontitis such as P. gingivalis (basic verification)
• Potent antimicrobial and toxin-inhibitory activity: Produced antimicrobial substances, including bacteriocins, that directly combat periodontal pathogens and effectively neutralize virulence factors of harmful bacteria (in vitro verification)
• Regulation of inflammatory and osteoclastic responses: Reduced the production of a broad range of inflammatory and osteoclastogenic (bone-resorbing) cytokines released from gingival tissue due to pathogen-host interactions
• Oral lesion colonization and oral health improvement: Beneficial bacteria successfully colonized oral lesion sites, alleviating periodontitis symptoms and improving overall oral health (periodontitis animal model)

In vitro and animal model analyses demonstrated that L. lactis and S. thermophilus probiotics are effective in preventing and treating oral diseases such as periodontitis by inhibiting the growth of periodontal pathogens and attenuating oral inflammatory responses.

It may help alleviate bad breath with a dual mechanism of inhibiting halitosis bacteria and neutralizing malodorous compounds (sulfur compounds).

It may help improve oral health by inhibiting cariogenic bacteria (Streptococcus mutans) and interfering with their adhesion to tooth surfaces.