Akkermansia muciniphila Alleviates Porphyromonas gingivalis-induced Periodontal Disease by Enhancing Bacterial Clearance

This study is to investigate the role of Akkermansia muciniphila (Am) in enhancing immune defense against Porphyromonas gingivalis (Pg)-induced periodontal disease. Twenty C57BL/6 J mice received 50 µL of Pg suspension (1.5 × 10⁹ CFU/mL) with or without 50 µL of Am suspension (1.5 × 10⁹ CFU/mL) orally every 2 days for a total of 18 administrations to assess bone resorption and inflammation. Gingival cervical fluid and periodontal plaques were collected for microbiota analysis using 16S sequencing. THP-1 (a human leukemia monocytic cell line) differentiated macrophages were used to explore the underlying beneficial mechanisms of Am by evaluating gene expression, cytokine production, and phagocytosis activity. Am administration attenuated alveolar bone loss and reduced inflammation in Pg-induced periodontitis in mice. Microbiota analysis revealed that Am reduced bacterial load and modified the composition of periodontal microbiota. In THP-1 macrophages, Am enhanced the phagocytosis of Pg by restoring MyD88 protein levels. RNA sequencing and western blotting results showed that Am upregulated TLR2 and MyD88 expression while downregulating C5aR, indicating interference with the TLR2-C5aR-MyD88 interplay. Am enhances immune defense against Pg-induced periodontal disease by modulating the TLR2-C5aR-MyD88 signaling pathway. These findings suggest that Am could be a promising therapeutic option for managing periodontal disease.