P. gingivalis alters lung microbiota and aggravates disease severity of COPD rats by up-regulating Hsp90α/MLKL

ABSTRACT

Background

Epidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear.

Methods and Results

A COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90α/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90α and MLKL in serum and lung tissue verified that Hsp90α/MLKL was up-regulated.

Conclusion

These results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90α/MLKL might participate in.

KEYWORDS:

• Porphyromonas gingivalis
• chronic obstructive pulmonary disease
• lung microbiota
• Hsp90α
• MLKL
• necroptosis

Acknowledgments

We sincerely thank Yanqing Liu (School and Hospital of Stomatology, China Medical University), Xin Qiao (Department of Pulmonary and Critical Care Medicine, the First Hospital of China Medical University) and HaoShen Feng (Shengjing Hospital of China Medical University) for providing key technical support for this experiment.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/20002297.2024.2334588

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81700970], [82170969] and [82101027], Doctoral Research Foundation of Liaoning Province [2021-BS-01].