Crosstalk between iron metabolism dysregulation and the oral microbiome in periodontitis.

Background: Periodontitis is a chronic inflammatory disease caused by periodontal pathogens. The impact of periodontitis is not only limited to the oral cavity, but also related to a variety of systemic diseases. Iron is a kind of redox metal, which may be deleterious to cells by producing damaging free radicals. Iron homeostasis dysregulation, especially ferroptosis, involves in the progression of periodontitis. Objective: This review aims to systematically summarize the crosstalk between iron metabolism dysregulation and the oral microbiome in periodontitis, focusing on alterations in iron-related biomarkers, iron-mediated tissue damage, the role of ferroptosis, and the potential of iron-targeted therapies. Design: A narrative review of recent advances in iron metabolism and ferroptosis, with emphasis on studies investigating molecular mechanisms, clinical correlations, and therapeutic interventions in periodontitis. Results: In periodontitis, serum iron and transferrin levels are decreased, while ferritin, hepcidin, and ceruloplasmin are elevated. Dysregulated iron metabolism promotes periodontal pathogen survival, amplifies inflammatory responses, induces ferroptosis in periodontal ligament cells, and contributes to alveolar bone resorption. Iron disorders also link periodontitis to systemic diseases such as anemia of inflammation, type 2 diabetes, and cardiovascular disease. Preclinical studies show that iron chelators (e.g. deferoxamine) and lactoferrin can inhibit bacterial growth, alleviate ferroptosis, and promote periodontal regeneration. Conclusions: Iron metabolism dysregulation and ferroptosis play critical roles in the initiation and progression of periodontitis and its systemic comorbidities. Targeting iron homeostasis represents a promising therapeutic strategy, but further well-designed clinical trials are needed to validate efficacy and safety.