Microencapsulatedalleviates acute lung injury in juvenile mice by protecting intestinal barrier.

Abstract

INTRODUCTION: The gut-lung axis plays a critical role in the pathogenesis of acute lung injury (ALI). While intestinal microbiota, particularly(AKK), has been linked to the regulation of ALI in adult murine model, its impact on juvenile hosts, who exhibit heightened susceptibility to lipopolysaccharide (LPS)-induced ALI, remains poorly understood. Moreover, despite microencapsulation enhancing the probiotic gastrointestinal survival and colonization of probiotics, the therapeutic potential of microencapsulated AKK (AKK-MC) in juvenile murine ALI has not been explored. METHODS: In this study, juvenile mice were orally gavaged with live AKK or AKK-MC for 14 days, with LPS-induced ALI established on day 11. Lung tissues were analyzed for morphological changes and inflammatory cytokine analysis. Bronchoalveolar lavage fluid (BALF) was collected for total cell counts and protein concentration. Macrophages and neutrophils infiltration in the lungs was quantified via immunofluorescence staining. Four segments of the intestinal tract (jejunum, ileum, cecum, and colon) were harvested for histological analysis using hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff (AB-PAS), and toluidine blue (TBO) staining. These evaluations included measurements of villus height to crypt depth, intestinal injury scoring, and counts of goblet and mast cells. RESULTS: AKK-MC treatment resulted in higher fecal abundance of AKK compared to AKK group. AKK treatment attenuated LPS-induced weight loss and mitigated lung damage. This was evidenced by reduced protein concentration and cell counts in BALF, downregulation ofandexpression, improved lung histology, and decreased macrophage infiltration and neutrophil extracellular traps formation. In the intestine, AKK treatment restored mucosal architecture, increased villus height to crypt depth ratios, maintained goblet cell populations, and reduced mast cell infiltration across intestinal segments. CONCLUSION: These results demonstrate that microencapsulation enhances AKK's efficacy in ameliorating LPS-induced ALI in juvenile mice through gut microbiota modulation. This study provides a crucial foundation for the development of probiotic-based interventions in pediatric ALI.