Porphyromonas gingivalis Promotes Glioma Progression via the PI3K/AKT/mTOR Signaling Pathway

Glioma is the most prevalent and aggressive brain tumor with high recurrence rates and poor survival. Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, has emerged as a potential contributor to neurological diseases. However, whether P. gingivalis is present in glioma tissues and directly promotes malignant progression remains unclear. Here, immunohistochemistry the detected gingipain in 11 of 13 human glioma specimens, while fluorescence in situ hybridization further detected P. gingivalis-targeted 16S rRNA signals in 3 of 13 specimens. These findings support the presence of P. gingivalis-associated signals in human glioma tissues. In cellular models, P. gingivalis invaded glioblastoma cells and promoted cell proliferation, migration, and invasion through induction of mesenchymal transition and extracellular matrix remodeling, thereby accelerating glioma progression. In a mouse xenograft model, P. gingivalis inoculation enhanced tumor growth and was associated with changes in proliferation, mesenchymal transition, and ECM remodeling-related markers. Mechanistically, P. gingivalis activated the PI3K/AKT/mTOR signaling pathway, while pharmacological AKT inhibition (AKTi-1/2) effectively suppressed these tumor-promoting effects. Metronidazole treatment also reduced tumor growth in vivo. Collectively, these findings identify P. gingivalis as a potential microbial contributor to glioma malignant progression and support further investigation of host–microbe interactions and AKT signaling as potential avenues for therapeutic research.