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

Teodora Nicola, Nancy Wenger, Xin Xu, Michael Evans, Luhua Qiao, Gabriel Rezonzew, Youfeng Yang, Tamas Jilling, Camilla Margaroli, Kristopher Genschmer, Kent Willis, Namasivayam Ambalavanan, J. Edwin Blalock, Amit Gaggar and Charitharth Vivek Lal ()
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Teodora Nicola: University of Alabama at Birmingham
Nancy Wenger: University of Alabama at Birmingham
Xin Xu: University of Alabama at Birmingham
Michael Evans: University of Alabama at Birmingham
Luhua Qiao: University of Alabama at Birmingham
Gabriel Rezonzew: University of Alabama at Birmingham
Youfeng Yang: University of Alabama at Birmingham
Tamas Jilling: University of Alabama at Birmingham
Camilla Margaroli: University of Alabama at Birmingham
Kristopher Genschmer: University of Alabama at Birmingham
Kent Willis: University of Alabama at Birmingham
Namasivayam Ambalavanan: University of Alabama at Birmingham
J. Edwin Blalock: University of Alabama at Birmingham
Amit Gaggar: University of Alabama at Birmingham
Charitharth Vivek Lal: University of Alabama at Birmingham

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.

Date: 2024
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DOI: 10.1038/s41467-024-51169-0

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