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Background <p>Periodontitis is a complex polymicrobial disease driven by synergistic interactions within a dysbiotic oral community. Within this network, <i>Porphyromonas gingivalis</i> acts as a keystone pathogen that orchestrates the pathogenic transformation of the microbiota. Current broad-spectrum antimicrobials often disrupt the entire microbial ecosystem and release immunogenic lipopolysaccharides (LPS). We aimed to develop a targeted approach, Near-Infrared Photo-Antibacterial Targeting Therapy (NIR-PAT<sup>2</sup>), using an antibody-photosensitizer conjugate (IgY-IR700) to reduce <i>P. gingivalis</i> load within this polymicrobial complex and modulate the community profile.</p> Methods <p>We evaluated the binding and bactericidal mechanism of NIR-PAT<sup>2</sup> in vitro compared to antimicrobial photodynamic therapy (aPDT), using scanning electron microscopy (SEM) and endotoxin assays. In vivo, a ligature-induced periodontitis mouse model was used to assess therapeutic effects on alveolar bone resorption and microbiome community structure (16&#xa0;S rRNA sequencing).</p> Results <p>In vitro, NIR-PAT<sup>2</sup> eliminated <i>P. gingivalis</i> without affecting human cells. SEM analysis revealed a distinct mechanism: unlike aPDT, which caused bacterial disintegration, NIR-PAT<sup>2</sup> induced lethal transmembrane perforations while maintaining structural integrity. In parallel, endotoxin assays demonstrated that NIR-PAT<sup>2</sup> treatment significantly suppressed LPS release compared to aPDT. In vivo, NIR-PAT<sup>2</sup> treatment significantly inhibited alveolar bone resorption. Crucially, microbiome analysis demonstrated that NIR-PAT<sup>2</sup> did not merely eliminate the environment but induced a compositional shift toward a health-associated profile. By suppressing <i>Porphyromonas</i>, the treatment facilitated the partial restoration of commensal genera such as <i>Streptococcus</i>, disrupting the dysbiotic network.</p> Conclusions <p>This study suggests that NIR-PAT<sup>2</sup> functions as a “Near-Infrared Photo-Bacterialflora Modulation (NIR-PBAM)” technology. By targeting a keystone pathogen within the polymicrobial community, NIR-PBAM offers a strategy to partially restore microbial balance while presenting a potential advantage in limiting LPS release, thus overcoming the ecological disruption caused by conventional broad-spectrum antimicrobials.</p> Graphical Abstract <p></p>

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Near infrared photo-bacterialflora modulation technology realized controlling periodontitis: modulation of disease-associated dysbiosis in oral microbiota using near infrared photo-antibacterial targeting therapy (NIR-PAT2)

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Hiroshi Maruyama,
  • Kazuhide Sato,
  • Kiyoshi Sakai,
  • Hirotoshi Yasui,
  • Ryu Okada,
  • Li Xinheng,
  • Koji Umeda,
  • Shofiqur Rahman,
  • Van Sa Nguyen,
  • Hideharu Hibi

摘要

Background

Periodontitis is a complex polymicrobial disease driven by synergistic interactions within a dysbiotic oral community. Within this network, Porphyromonas gingivalis acts as a keystone pathogen that orchestrates the pathogenic transformation of the microbiota. Current broad-spectrum antimicrobials often disrupt the entire microbial ecosystem and release immunogenic lipopolysaccharides (LPS). We aimed to develop a targeted approach, Near-Infrared Photo-Antibacterial Targeting Therapy (NIR-PAT2), using an antibody-photosensitizer conjugate (IgY-IR700) to reduce P. gingivalis load within this polymicrobial complex and modulate the community profile.

Methods

We evaluated the binding and bactericidal mechanism of NIR-PAT2 in vitro compared to antimicrobial photodynamic therapy (aPDT), using scanning electron microscopy (SEM) and endotoxin assays. In vivo, a ligature-induced periodontitis mouse model was used to assess therapeutic effects on alveolar bone resorption and microbiome community structure (16 S rRNA sequencing).

Results

In vitro, NIR-PAT2 eliminated P. gingivalis without affecting human cells. SEM analysis revealed a distinct mechanism: unlike aPDT, which caused bacterial disintegration, NIR-PAT2 induced lethal transmembrane perforations while maintaining structural integrity. In parallel, endotoxin assays demonstrated that NIR-PAT2 treatment significantly suppressed LPS release compared to aPDT. In vivo, NIR-PAT2 treatment significantly inhibited alveolar bone resorption. Crucially, microbiome analysis demonstrated that NIR-PAT2 did not merely eliminate the environment but induced a compositional shift toward a health-associated profile. By suppressing Porphyromonas, the treatment facilitated the partial restoration of commensal genera such as Streptococcus, disrupting the dysbiotic network.

Conclusions

This study suggests that NIR-PAT2 functions as a “Near-Infrared Photo-Bacterialflora Modulation (NIR-PBAM)” technology. By targeting a keystone pathogen within the polymicrobial community, NIR-PBAM offers a strategy to partially restore microbial balance while presenting a potential advantage in limiting LPS release, thus overcoming the ecological disruption caused by conventional broad-spectrum antimicrobials.

Graphical Abstract