Asthma manifests as a systemic inflammatory condition with cross-organ implications, particularly involving respiratory and gastrointestinal systems through the lung-gut axis. This study investigated probiotic-mediated modulation of inflammatory responses in a lipopolysaccharide (LPS)-enhanced fumigation-induced asthma rat model, emphasizing TLR4/NF-κB pathway dynamics. Experimental protocols combined airway LPS administration with ovalbumin sensitization to simulate chronic inflammation, followed by probiotic supplementation. Histopathological analysis via hematoxylin-eosin (HE) staining demonstrated severe airway epithelial disruption in asthmatic rats, which were significantly ameliorated post-probiotic intervention. Quantitative assessments revealed probiotics’ dual regulatory effects: systemic inflammation markers (serum IL-6, TNF-α, IL-1β) and lung-specific mucin MUC5AC were downregulated, while intestinal barrier integrity marker MUC2 in colon tissue was upregulated. Mechanistic exploration identified suppressed TLR4 and NF-κB protein expression in both lung and colon tissues, indicating pathway-wide inhibition. Probiotics restored alveolar structural integrity and reduced inflammatory cell infiltration in lung parenchyma. These findings suggest probiotics mitigate asthma-associated inflammation through multi-organ crosstalk, targeting shared molecular pathways across the lung-gut axis. The observed TLR4/NF-κB suppression aligns with reduced cytokine storm activity, highlighting probiotics’ capacity to disrupt pro-inflammatory signaling cascades. Furthermore, the differential regulation of mucins (MUC5AC vs. MUC2) underscores tissue-specific therapeutic effects, balancing airway hypersecretion and intestinal barrier fortification. This study advances the paradigm of probiotics as pleiotropic agents in chronic respiratory disease management, offering a novel strategy to address systemic inflammation beyond conventional bronchodilator therapies. By elucidating mechanistic links between gut microbiota modulation and pulmonary inflammation resolution, our work supports translational applications of probiotics in asthma and related comorbidities, advocating for integrative approaches in precision medicine frameworks.

KEY WORDS: Probiotic; Lung-gut axis; Asthma; TLR4; NF-κB; Inflammatory.

CHEN, Y.; REN, X. & PANG, C. Adjunctive probiotics alleviate asthmatic symptoms via modulating the gut-lung axis in animal model: A biochemical, molecular, and histopathological approach. Int. J. Morphol., 44(2):451-462, 2026.