Int J Mol Sci. 2026 Apr 23. pii: 3759. [Epub ahead of print]27(9):
Genetically modified (GM) lactic acid bacteria (LAB) are gaining attention as tools for innovation in the food sector, health applications, and industrial processes. LAB have long been used safely due to their GRAS/QPS status, making them suitable for improving fermentation and synthesizing specific and beneficial metabolites. Advances in genomics and gene editing have significantly expanded the available tools, ranging from classical mutagenesis to site-specific recombination, homologous recombination in non-coding regions, CRISPR-based systems, and food-grade chromosomal integration. These approaches enable the insertion of desired genes and the development of engineered strains with tailored functionalities. GM-LAB are also being studied as live delivery systems for therapeutic molecules, including cytokines, hormones, antimicrobial peptides, and vaccine antigens. Engineered strains of Lactococcus lactis and Lactobacillus spp. have yielded promising outcomes in applications such as mucosal immunization, modulation of inflammatory and metabolic responses, and inhibition of pathogenic microorganisms, including multidrug-resistant bacteria. From an industrial perspective, several studies highlight their potential for cost-effective recombinant protein production and the synthesis of high-value metabolites through fermentation. However, within the European Union, their use is subject to stringent regulatory oversight, requiring comprehensive molecular and environmental risk assessments, careful evaluation of horizontal gene transfer, and a preference for markerless chromosomal integrations. Despite these constraints, GM-LAB offer significant potential to improve food quality, sustainability, and human health.
Keywords: EU regulation; genetically modified microorganisms; genome editing; lactic acid bacteria; new breeding techniques; probiotic engineering; risk assessment; synthetic biology