2. Academic Validation
  3. Inactivated Bacillus subtilis R0179 Inhibits Porphyromonas Gingivalis-Induced Gingival Inflammation Via TLR2/NF-κB Signaling in a Murine Model of Periodontitis

Inactivated Bacillus subtilis R0179 Inhibits Porphyromonas Gingivalis-Induced Gingival Inflammation Via TLR2/NF-κB Signaling in a Murine Model of Periodontitis

  • Inflammation. 2025 Aug 8. doi: 10.1007/s10753-025-02348-8.
Weiwei Zhao 1,  Lingli Ji 1,  Jie Li 1,  Dandan Liu 1,  Chenying Zhang 1,  Xiaozhe Wang 1,  Yang Liu 2,  Shuguo Zheng 3
Affiliations

Affiliations

  • 1 Department of Preventive Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, 100081, PR China.
  • 2 Department of Preventive Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, 100081, PR China. liuyang0369@126.com.
  • 3 Department of Preventive Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, 100081, PR China. kqzsg86@bjmu.edu.cn.
PMID: 40779055 DOI: 10.1007/s10753-025-02348-8
Abstract

This study aims to explore the mechanism by which heat-inactivated Bacillus subtilis (B. subtilis) R0179 modulates the TLR2/NF-κB signaling pathway to inhibit Porphyromonas gingivalis (P. gingivalis) induced gingival inflammation. In vitro experiments showed that P. gingivalis could invade gingival epithelial cells within 2 h of Infection, as observed by transmission electron microscopy, and Infection with P. gingivalis upregulated the expression of TLR1, TLR2, TLR4, TLR6, and p-NF-κB in gingival epithelial cells while promoting the release of IL-1β, IL-6, and TNF-α. The addition of heat-inactivated B. subtilis R0179 during P. gingivalis Infection inhibited the expression of TLR2, TLR4, and p-NF-κB and suppressed the release of IL-1β, IL-6, and TNF-α. In vivo experiments using a mouse model of P. gingivalis-induced experimental periodontitis confirmed these findings, with heat-inactivated B. subtilis R0179 application reducing gingival inflammation, as observed by Hematoxylin and Eosin staining, and downregulating TLR2, TLR4, p-NF-κB, IL-1β, IL-6, and TNF-α signals, as detected by immunohistochemistry. Further investigation using TLR2 and TLR4 agonists revealed that TLR2 receptor agonists antagonized the B. subtilis R0179-induced downregulation of p-NF-κB, IL-6, IL-1β, and TNF-α. These results suggest that B. subtilis R0179 may inhibit P. gingivalis-induced gingival inflammation by suppressing the TLR2/NF-κB signaling pathway, consequently decreasing the production of pro-inflammatory cytokines.

Keywords

Bacillus subtilis; Porphyromonas gingivalis; Inflammation; Periodontitis; Toll-like Receptors.

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