Pseudomonas aeruginosa remains a major clinical threat, particularly in patients with chronic lung disease and those who are critically ill. Treatment failure is increasingly common not only because of intrinsic and acquired antimicrobial resistance but also due to bacterial strategies that limit antibiotic effectiveness. In particular, biofilm formation and the presence of persister cell populations promote persistent, refractory infections that conventional antibiotics often cannot eradicate.
Lacticaseibacillus rhamnosus has been identified as a source of multiple bioactive factors capable of interfering with P. aeruginosa pathogenesis at different stages. The review summarizes experimental evidence that L. rhamnosus exerts antimicrobial activity through several complementary mechanisms rather than a single mode of action. These include production of organic acids that alter local pH, secretion of low–molecular-weight metabolites with inhibitory effects, and enzymatic activities that may degrade or modify bacterial structures involved in adhesion and community formation.
Among the active properties described, biosurfactant production by L. rhamnosus is highlighted as a mechanism that can disrupt microbial adhesion and impair biofilm development. Enzymatic activities and small metabolites produced by the bacterium also contribute to interference with P. aeruginosa colonization and biofilm maturation. The cumulative action of these products can reduce bacterial adherence to surfaces and weaken established biofilm architecture, potentially making P. aeruginosa more susceptible to host defenses and co-administered antimicrobials.
Beyond direct antimicrobial effects, interactions between L. rhamnosus and host epithelial cells are reported to influence the host response. The organism may modulate inflammatory signaling and enhance mucosal defenses, which could contribute to limiting P. aeruginosa colonization and tissue invasion. These modulatory effects suggest a dual role for L. rhamnosus: direct antagonism of the pathogen and indirect support of host barrier and immune functions.
Cell-free supernatant (CFS) derived from L. rhamnosus cultures retains many of the antimicrobial and anti-biofilm properties attributed to the live organism. The review proposes that CFS and related postbiotic preparations may offer a safer alternative to administration of live probiotics, particularly in vulnerable patient populations where probiotic safety is a concern. However, the review also notes that preparations are variable across studies and that active constituents are incompletely characterized.
Despite consistent experimental findings supporting multi-target activity of L. rhamnosus against P. aeruginosa, important limitations remain. Key issues include variability in strain selection across studies, lack of standardized methods for preparing and reporting CFS or postbiotic products, and incomplete biochemical identification of the active compounds responsible for observed effects. These gaps hamper reproducibility and translational progress and are identified as priorities for future mechanistic and formulation work.
Clinical studies to date provide suggestive but limited evidence that L. rhamnosus–based interventions can reduce colonization or lower the incidence of ventilator-associated pneumonia associated with P. aeruginosa. The review emphasizes that while these findings are promising, robust clinical validation—ideally through standardized preparations and well-designed randomized trials—is still lacking. The authors position L. rhamnosus as a potential adjunctive strategy to conventional antimicrobial therapies rather than a standalone replacement.
The collective experimental and limited clinical evidence supports a conceptual role for Lacticaseibacillus rhamnosus in antagonizing Pseudomonas aeruginosa via multiple mechanisms: acidification, secreted metabolites, enzymes, biosurfactants, anti-biofilm effects, and modulation of host epithelial responses. To advance toward clinical application, the review calls for standardization of strains and cell-free preparations, detailed chemical and mechanistic characterization of active molecules, and rigorous clinical studies to determine efficacy and safety in target patient populations. Until such validation is available, L. rhamnosus–derived approaches should be regarded as promising adjuncts that require further development rather than established clinical treatments.