A lactobacilli-based inhaled live biotherapeutic product attenuates pulmonary neutrophilic inflammation

Area of Science:

• Pulmonary Medicine
• Microbiology
• Inflammation Research

Background:

• Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants, linked to adult chronic obstructive pulmonary disease (COPD) due to shared features like lung degradation and neutrophil influx.
• Both BPD and COPD exhibit altered lung microbiota, specifically a depletion of firmicutes, but the role of bacteria in disease progression is unclear.
• The acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity are implicated in BPD development.

Purpose of the Study:

• To investigate the role of the Ac-PGP pathway in BPD development.
• To evaluate an inhaled live biotherapeutic (LBP) containing Lactobacillus strains for treating BPD and COPD models.
• To elucidate the therapeutic mechanisms of LBPs in chronic lung diseases.

Main Methods:

• Utilized murine models to study BPD development and the effects of Ac-PGP.
• Conducted gain- and loss-of-function studies to determine Ac-PGP's role in BPD.
• Tested an inhaled Lactobacillus-based LBP in vitro and in vivo models of BPD and COPD.

Main Results:

• Ac-PGP was found to play a critical role in driving BPD development.
• The Lactobacillus-based LBP significantly improved lung structure and function in BPD and COPD models.
• LBP treatment mitigated neutrophil influx and reduced pro-inflammatory markers via the MMP-9/PGP pathway.

Conclusions:

• Inhaled LBPs demonstrate therapeutic potential for chronic lung diseases like BPD and COPD.
• Targeting the MMP-9/PGP pathway with Lactobacillus offers a promising strategy for managing lung inflammation and degradation.
• LBPs may address common disease progression mechanisms applicable to various chronic pulmonary conditions.