Lacticaseibacillus paracasei ATG-E1 Alleviates Particulate Matter-Induced Airway Inflammation in Association with Altered Inflammatory Signaling, Gut Microbiota, and Fecal Metabolites.

Particulate matter (PM) acts as an environmental trigger for inflammatory airway diseases. This study investigated whether oral administration of Lacticaseibacillus paracasei ATG-E1 could therapeutically attenuate PM10 diesel exhaust particle (PM10D)-induced airway inflammation, and explored associated changes in inflammatory signaling, gut microbiota, and fecal metabolites. BALB/c mice were intranasally challenged with PM10D on days 0, 3, 6, and 8, and treated with ATG-E1 or dexamethasone after airway inflammation had been induced. Airway inflammation was evaluated using bronchoalveolar lavage fluid (BALF) cytology, flow cytometry, histopathology, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction, and immunoblotting. Lung transcriptomics, cecal 16S rRNA profiling, and fecal metabolomics were performed, and antitussive and expectorant activities were assessed using ammonia-induced cough and phenol red secretion assays. ATG-E1 reduced inflammatory cell infiltration and neutrophilia in BALF, decreased collagen deposition, and lowered levels of pro-inflammatory mediators in BALF and lung tissue. ATG-E1 attenuated PM10D-activated IκBα and ERK phosphorylation, whereas JNK and p38 phosphorylation were not significantly altered by PM10D under the present experimental conditions. ATG-E1 also reduced caspase-1 and interleukin-1α expression. RNA sequencing revealed a broad downregulation of cytokine-cytokine receptor interaction signaling. ATG-E1 treatment was associated with gut microbiome remodeling, including enrichment of Enterorhabdus and Butyricicoccus, and altered fecal metabolite profiles were characterized by increased branched-chain fatty acids and decreased branched-chain amino acids. Functionally, ATG-E1 reduced cough frequency and increased tracheal phenol red output. Overall, L. paracasei ATG-E1 alleviated PM10D-induced airway inflammation and respiratory symptoms, in association with pulmonary immunomodulation and microbiome-associated fecal metabolite remodeling.