Biochemical and molecular mechanisms of probiotic action: current concepts and emerging therapeutic applications.

Abstract

Probiotic effects are mediated by a network of biochemical transformations and molecular signaling events that influence host physiology through local and systemic mechanisms. This review examines how probiotic microorganisms generate functional metabolites, including short-chain fatty acids, bile acid derivatives, and indole compounds, and how these molecules interact with host receptors and intracellular signaling pathways such as NF-κB, JAK/STAT, FXR, TGR5, AhR, and inflammasome-mediated signaling. In addition to metabolite-mediated signaling, probiotics may inhibit pathogens through organic acid production, bacteriocins, and quorum-quenching mechanisms, while also contributing to epithelial barrier integrity through modulation of tight-junction proteins and mucosal defenses. These interconnected pathways affect inflammation, metabolic regulation, host-microbe communication, and host defense against pathogens. The review further discusses pharmacomicrobiomic interactions, engineered probiotics, and emerging delivery technologies, highlighting the importance of strain specificity, host context, and microbiome composition in determining therapeutic outcomes. These findings underscore the importance of mechanistic frameworks for the rational development of targeted microbiome-based interventions.