Beyond probiotics: Lacticaseibacillus rhamnosus as a multi-target antagonist of Pseudomonas aeruginosa infections.

The increasing failure of antimicrobial therapies against Pseudomonas aeruginosa represents a major challenge in clinical practice, particularly in patients with chronic lung disease and critical illness. Beyond intrinsic and acquired resistance, biofilm formation and persister cell populations contribute to persistent and refractory infections, limiting the efficacy of conventional antibiotics. Lacticaseibacillus rhamnosus has emerged as a source of bioactive compounds capable of interfering with multiple stages of P. aeruginosa pathogenesis. Its antimicrobial activity involves organic acid production, secretion of low-molecular-weight metabolites, enzymatic effects, and biosurfactant-mediated disruption of adhesion and biofilm formation. In addition, interactions with host epithelial cells indicate a role in modulating inflammatory responses and enhancing mucosal defenses. Cell-free supernatant (CFS) retain many of these properties and may represent a safer alternative to live probiotic administration. Despite consistent experimental evidence, key limitations remain, including variability in strain selection, lack of standardization of cell-free preparations, and incomplete characterization of active compounds. Clinical studies suggest potential benefits in reducing colonization and ventilator-associated pneumonia, although robust evidence is still limited. These findings support the potential role of L. rhamnosus as an adjunctive strategy in the management of P. aeruginosa infections, while highlighting the need for mechanistic standardization and clinical validation.