FAs and their metabolites as antibacterial agents: mechanisms, food applications, and translational opportunities.

Abstract

Antimicrobial resistance and the demand for effective food-preservation strategies have increased interest in fatty acids (FAs) and their derivatives as potential antibacterial agents. FAs can affect bacterial membranes, cellular energetics, biofilm-associated phenotypes, and, in some organisms, specific metabolic pathways. However, these effects vary considerably with FA structure, concentration, ionization state, pH, formulation, bacterial species, and assay conditions. Additionally, microbiota-derived short-chain FAs may also contribute to host defense by influencing epithelial integrity, immune signalling, microbiome composition, and colonization resistance. Still, researchers should distinguish these indirect effects from direct bacterial killing. Evidence from laboratory media cannot necessarily predict performance in complex foods, where proteins, lipids, processing conditions, oxidation, and sensory limitations can alter antibacterial activity. Next, monoglycerides, conjugates, and delivery systems may improve stability or availability, although their efficacy, safety, and regulatory status require formulation-specific evaluation. This review critically examines direct antibacterial activity, host- and microbiome-mediated effects, food-matrix applications, resistance-related considerations, and emerging formulation approaches. Current evidence supports the potential of selected FAs in defined applications, while emphasizing the need for standardized assays, appropriate food-matrix validation, and stronger animal and human evidence.