Lactobacillus reuteri Alleviates Hyperoxia-Induced BPD by Activating IL-22/STAT3 Signaling Pathway in Neonatal Mice

Area of Science:

• Microbiology
• Immunology
• Neonatal Medicine

Background:

• Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in preterm infants.
• The role of lung microbiota, specifically Lactobacillus, in BPD pathogenesis and treatment remains largely unexplored.
• Understanding the mechanisms underlying BPD is crucial for developing effective interventions.

Purpose of the Study:

• To investigate the therapeutic effect of Lactobacillus reuteri on hyperoxia-induced lung injury in a mouse model.
• To elucidate the potential mechanism involving the IL-22/STAT3 signaling pathway.
• To explore the role of the L. reuteri metabolite indole-3-aldehyde (3-IAld) in BPD.

Main Methods:

• Intranasal administration of L. reuteri and 3-IAld in hyperoxia-exposed mice.
• Assessment of lung pathological changes and inflammatory cytokine levels (IL-1β, IL-6, TNF-α).
• Measurement of surfactant protein C (SPC), aquaporin 5 (AQP5), and VEGFR2 levels.
• Evaluation of IL-22 expression and its blockade using neutralizing antibodies.
• Confirmation of STAT3 activation in MLE-12 cells.

Main Results:

• L. reuteri and 3-IAld significantly ameliorated BPD-like lung changes in mice.
• Treatment reduced proinflammatory cytokines and increased levels of SPC, AQP5, and VEGFR2.
• L. reuteri and 3-IAld upregulated IL-22 expression.
• IL-22 administration alone improved lung pathology, and its protective effects were blocked by anti-IL-22 antibodies.
• IL-22 activated STAT3 signaling in lung epithelial cells.

Conclusions:

• L. reuteri alleviates hyperoxia-induced lung injury in a mouse model of BPD by activating the IL-22/STAT3 pathway.
• The probiotic L. reuteri, through IL-22 production, represents a potential therapeutic strategy for neonatal lung injury.
• Indole-3-aldehyde, a metabolite of L. reuteri, also demonstrates protective effects, highlighting its potential therapeutic role.