Porphyromonas gingivalis lipopolysaccharide increases blood-brain barrier permeability via ferroptosis

  • Arch Oral Biol. 2026 Jul 24:191:106700. doi: 10.1016/j.archoralbio.2026.106700.
Jinyang Li  1 ,  Sijia Zhang  2 ,  Qianqian Zhang  2 ,  Na Liu  1 ,  Jiayu Zhang  1 ,  Yazheng Wang  1 ,  Yue Chen  3
Affiliations
  • 1. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Jiaotong University, Xi'an 710000, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Jiaotong University, Xi'an 710000, China; Department of Periodontology, College of Stomatology, Xi'an Jiaotong University, Xi'an 710000, China.
  • 2. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Jiaotong University, Xi'an 710000, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Jiaotong University, Xi'an 710000, China.
  • 3. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Jiaotong University, Xi'an 710000, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Jiaotong University, Xi'an 710000, China; Department of Periodontology, College of Stomatology, Xi'an Jiaotong University, Xi'an 710000, China. Electronic address: [email protected].
PMID: 42546472 DOI: 10.1016/j.archoralbio.2026.106700
Abstract

Objectives: Ferroptosis, a newly characterized form of regulated cell death, has been associated with the dysfunction of the blood-brain barrier (BBB). Nevertheless, its precise role in BBB disruption caused by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) remains unclear.

Design: Experimental periodontitis was induced by injecting P. gingivalis LPS into the left and right sides of the palatal gingiva between the maxillary first and second molars every two days for eight weeks, then changes in brain tissue in BBB permeability, and ferroptosis‑related factors were assessed. Changes in BBB permeability and ferroptosis-related markers were re-evaluated in vitro.

Results: In vivo, sodium fluorescein deposition increased and tight junction (TJ) protein expression decreased in the P. gingivalis LPS group. P. gingivalis LPS-induced periodontitis reduced GPX4 and SLC7A11 expression in gingival tissues. Immunofluorescence results revealed that GPX4 and SLC7A11 protein levels were downregulated in cortical endothelial cells in the P. gingivalis LPS group. Western blotting revealed that ferrostatin-1 (Fer-1) significantly up-regulated GPX4 and SLC7A11 expression, thereby reducing hCMEC/D3 tight junction proteins loss induced by P. gingivalis LPS.

Conclusions: Ferroptosis may be a relevant mechanism underlying the link between P. gingivalis LPS and BBB disruption.

Keywords
Blood-brain barrier; Ferroptosis; Lipopolysaccharide; Porphyromonas gingivalis; periodontitis.
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