Porphyromonas gingivalis and Ferroptosis: Evidence, Limitations, and Significance

Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in periodontal dysbiosis and has been linked to multiple systemic diseases. Ferroptosis is a form of regulated cell death driven by iron-dependent lipid peroxidation, and accumulating evidence implicates it in P. gingivalis-associated tissue injury. This review examines the mechanisms and disease contexts linking P. gingivalis to ferroptosis across experimental models. In inflammatory and tissue-injury models, P. gingivalis exposure is associated with disrupted iron homeostasis, increased lipid peroxidation, and impaired antioxidant defenses. In contrast, tumor models show reduced ferroptotic sensitivity associated with P. gingivalis. These findings support a context-dependent model in which P. gingivalis may alter host-cell susceptibility to ferroptosis through direct bacterial effects and indirect changes in the microbial, inflammatory, and redox environment. This framework highlights how bacterial exposure, host-cell state, and the disease microenvironment shape ferroptotic responses and provides a basis for evaluating the mechanistic and translational significance of ferroptosis in P. gingivalis-associated diseases.