Microbial Extracellular Vesicles of Gut Microbiome: Implication on therapeutic Strategies

Abstract

Microbial extracellular vesicles (MEVs) originating from the gut microbiome are widely recognized as key mediators of host-microbe communication. These nanosized, spherical particles containing a complex cargo enclosed by a lipid membrane are capable of modulating human intestinal immunity, epithelial integrity and systemic physiology. MEV uptake by host cells occurs through multiple pathways, and the selectivity of these routes is determined by vesicular surface components as well as host cell receptor expression and microenvironmental conditions. Following internalisation, MEV-associated cargo is capable of extending their microbial signalling beyond localised intestinal interactions, contributing to systemic metabolic regulation, modulation of antibiotic resistance, reshaping innate and adaptive immune responses and bi-directional communication along the gut-brain axis. MEVs can facilitate immune evasion and contribute to pathogenesis, while they can also support immune tolerance and microbiota-driven homeostasis. Collectively, these mechanistic insights highlight the dualistic nature of MEVs. Interindividual variability in MEVs composition across microbial species and strains, coupled with host genetic and immunological heterogeneity, emphasizes a personalised dimension towards the effects of MEVs. Exploiting this variability presents promising opportunities for precision medicine. This review consolidates current knowledge of MEV origins across kingdom boundaries, diverse biogenesis routes (outer membrane vesicles, membrane vesicles and other variants) and conserved biology from prokaryotes to eukaryotes, along with the mechanistic pathways governing MEV uptake by host cells. It further evaluates established methodologies and emerging characterization techniques for MEVs, while addressing the key technical, and regulatory challenges shaping their translational potential of MEVs.