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

## TL;DR

This paper reviews how Lactobacillus cell-free supernatants, especially from Limosilactobacillus fermentum, can help combat antimicrobial resistance by inhibiting harmful bacteria and biofilms.

## Contribution

The study systematically evaluates the antimicrobial and antibiofilm potential of Limosilactobacillus fermentum cell-free supernatants as a sustainable alternative to antibiotics.

## Key findings

- Limosilactobacillus fermentum cell-free supernatants show strong antimicrobial activity against multidrug-resistant pathogens.
- The supernatants effectively inhibit biofilm formation and demonstrate physicochemical stability for practical applications.
- They are positioned as a scalable and eco-friendly solution to address antimicrobial resistance within a One Health framework.

## Abstract

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 Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae. In this context, Lactobacillus-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 Limosilactobacillus fermentum. 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. L. fermentum 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 L. fermentum cell-free derivatives, supporting their safety and scalability for applied use. This review highlights L. fermentum 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.