Probiotic cell-free supernatants as a strategy against antimicrobial resistance: a systematic review

Antimicrobial resistance (AMR) is a critical global health threat that may cause up to 10 million deaths annually by 2050, requiring integrated actions within the One Health framework. The misuse of antimicrobials across human, animal, and environmental sectors has intensified the spread of multidrug-resistant bacteria, including <i>Escherichia coli, Staphylococcus aureus</i>, and <i>Klebsiella pneumoniae</i>. In this context, <i>Lactobacillus</i>-derived postbiotics have emerged as eco-friendly alternatives with antimicrobial and antibiofilm properties. A systematic review was conducted to consolidate scientific evidence on the strategic potential of Lactobacillus cell-free supernatants, with a specific focus on <i>Limosilactobacillus fermentum</i>. Studies published between 2000 and July 2025 were screened, prioritizing investigations that evaluated antimicrobial activity, biofilm inhibition, and efficacy in biological and technological models against multidrug-resistant pathogens. After screening, 95 studies were included in the analysis. <i>L. fermentum</i> was deliberately selected as the focus species based on consistent evidence of postbiotic efficacy against pathogenic bacteria and biofilm formation. The reviewed studies also demonstrated favorable physicochemical stability of <i>L. fermentum</i> cell-free derivatives, supporting their safety and scalability for applied use. This review highlights <i>L. fermentum</i> as a strategic model within One Health aligned approaches to combat AMR. The findings reinforce the role of postbiotics as sustainable, effective, and scalable tools for mitigating antimicrobial resistance across human, animal, and environmental interfaces.