Asthma is a common respiratory disease characterized by chronic inflammation and airway obstruction, with airway epithelial damage playing a pivotal role in pathogenesis. Existing treatments regulate inflammation without addressing epithelial barrier repair, indicating the need for therapeutic agents that target damaged epithelial cells. This study evaluates the effects of bacterial cellulose (BC), a biocompatible polymer with anti-inflammatory and pro-regenerative properties, as a promising therapeutic candidate for asthma. In a mouse model of house dust mite (HDM)-induced allergic asthma, intranasal BC administration markedly reduces both airway inflammation and mucus hypersecretion while also improving epithelial barrier integrity. Bronchoalveolar lavage fluid (BALF) metabolomics and single-cell RNA sequencing of human asthmatic epithelium samples reveal that BC downregulates epithelial CDP-diacyl glycerol synthase 1 (CDS1), resulting in decreased synthesis of phosphatidylinositol (PI) and PI 4,5- bisphosphate (PI(4,5)P₂) and suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling. CDS1 overexpression reverses the effect of BC on asthma in vivo, confirming that CDS1 is a key target. BC administration alleviates asthma by repairing the epithelial barrier and inhibiting PI3K/AKT signaling via CDS1-dependent PI reprogramming. Thus, treatment with BC represents a promising therapeutic strategy for asthma, with dual actions in repairing epithelial barrier dysfunction and mitigating inflammation.
Keywords: Airway epithelium; Asthma; Bacterial cellulose; CDP-diacyl glycerol synthase 1; Metabolic reprogramming; PI3K/AKT pathway.
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