Extracellular vesicles (EVs) are nanosized lipid bilayer-delimited particles secreted from almost all types of cells including bacteria, mammals and plants, which are presumed to be mediators of intercellular communication [1], [2], [3], [4]. EVs possess a functional versatility that extends beyond their conventional role as waste carriers. The current focus of interest in the field of EVs centers on their ability to mediate intercellular crosstalk of diverse cargo molecules, ranging from nucleic acids, and lipids to proteins [4], [5], [6], [7], [8]. In this regard, EVs have the potential to serve as amplifiers of signaling mechanisms during both normal cell homeostasis and pathological development [9].

In the 1960s, bacterial extracellular vesicles (BEVs) were first observed in Escherichia coli (E. coli). Subsequently, extensive research focused on BEVs has aimed to elucidate the mechanisms underlying their biogenesis, composition, and functional properties. BEVs are nanoparticles with diverse diameters, ranging from 20 to 400 nm. BEVs are composed of soluble microbial metabolites, including nucleic acids, proteins, lipoglycans, short-chain fatty acids (SCFAs), and quorum sensing peptides, which are endowed with the ability to protect bacteria against bacteriophages, form and maintain bacterial communities, and modulate the host immune system [10], [11], [12], [13]. Recently, accumulating evidence has supported the notion that microbial-derived EVs can serve as an important orchestrator in the mutual communications between gut microbiota and the host [14]. BEVs produced by gut microbiota can translocate to systemic circulation to control host metabolism, epithelial barrier integrity and immune responses [15]. In this regard, BEVs are potentially promising therapeutic modalities for use in vaccines, cancer immunotherapy regimens, and drug delivery cargos.

Plant-derived EVs (PEVs), such as EVs derived from herbal medicines, can be absorbed by the gut microbiota and influence the composition and homeostasis of gut microbiota. Owing to the pivotal role of the gut microbiota in maintaining the host physiological state, its dysbiosis can lead to a wide range of disorders, such as cancer and neurological and metabolic disorders. Ginger-derived EVs can be selectively taken up by Lactobacillaceae in a lipid-dependent manner in vivo, and the increased Lactobacillus abundance in turn enhances gut barrier integrity and alleviates colitis by producing indole-3-carboxaldehyde (I3A) to induce the secretion of IL-22 [16]. Thus, it is tempting to surmise that EVs may be an important mediator among the host, gut microbiota, and plants, such as diets or traditional Chinese medicines (TCMs).

In this review, we mainly highlight and discuss the roles of BEVs and PEVs and aim to provide new insight regarding the crosstalk among herbal medicine, gut bacteria and hosts. We surmise that EVs are crucial messengers between the gut microbiota and host, and that EVs represent a new approach to revealing the mechanism of herbal medicines.