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

Abstract

<p> <span>This study is to investigate the role of </span><em>Akkermansia muciniphila</em><span> (</span><em>Am</em><span>) in enhancing immune defense against </span><em>Porphyromonas gingivalis</em><span> (</span><em>Pg</em><span>)-induced periodontal disease. Twenty C57BL/6 J mice received 50 µL of </span><em>Pg</em><span> suspension (1.5 × 10</span>⁹<span> CFU/mL) with or without 50 µL of </span><em>Am</em><span> suspension (1.5 × 10</span>⁹<span> 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 </span><em>Am</em><span> by evaluating gene expression, cytokine production, and phagocytosis activity. </span><em>Am</em><span> administration attenuated alveolar bone loss and reduced inflammation in </span><em>Pg</em><span>-induced periodontitis in mice. Microbiota analysis revealed that </span><em>Am</em><span> reduced bacterial load and modified the composition of periodontal microbiota. In THP-1 macrophages, </span><em>Am</em><span> enhanced the phagocytosis of </span><em>Pg</em><span> by restoring MyD88 protein levels. RNA sequencing and western blotting results showed that </span><em>Am</em><span> upregulated TLR2 and MyD88 expression while downregulating C5aR, indicating interference with the TLR2-C5aR-MyD88 interplay. </span><em>Am</em><span> enhances immune defense against </span><em>Pg</em><span>-induced periodontal disease by modulating the TLR2-C5aR-MyD88 signaling pathway. These findings suggest that </span><em>Am</em><span> could be a promising therapeutic option for managing periodontal disease.</span> <br></p>