| Summary: | Therapy of lung infections sustained by <i>Pseudomonas aeruginosa</i> in cystic fibrosis (CF) patients is challenging due to the presence of a sticky mucus in the airways and the ability of the bacterium to form biofilm, which exhibits increased antibiotic tolerance. A lung-directed bacteriotherapy through the airway administration of probiotics could represent an alternative approach to probiotic diet supplementation to improve the benefits and clinical outcomes of this kind of intervention in CF patients. This study aims to evaluate the ability of probiotic strains to grow in artificial sputum medium (ASM), mimicking the CF lung microenvironment, and to affect the planktonic and biofilm growth of CF clinical strains of <i>P. aeruginosa</i> in the same conditions. The results demonstrate that <i>Lacticaseibacillus rhamnosus</i> and <i>Lactiplantibacillus plantarum</i> (LP) can grow in ASM. LP inhibited the planktonic growth of <i>P. aeruginosa</i>, while both lactobacilli reduced the pre-formed biofilm of <i>P. aeruginosa</i>. Interestingly, LP was demonstrated to reduce the amount of polysaccharides in the extracellular matrix of <i>P. aeruginosa</i> biofilms and to potentiate the antibiofilm effects of tobramycin. Overall, the results indicated that LP is a promising candidate as an adjuvant in the antimicrobial therapy of <i>P. aeruginosa</i> infections in CF patients.
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