Oral–Gut Microbial Crosstalk and Therapeutic Applications of Bacterial Extracellular Vesicles

With the accelerating trend of global population aging, oral and gut diseases are imposing a rising socioeconomic burden, both of which have well-known connections to microbial dysbiosis. As the gateway to the human body, the oral cavity exhibits close interactions with the gastrointestinal tract, which includes translocation of bacteria and bacterial extracellular vesicles (BEVs), as well as intermucosal immunity and neural signaling. These oral-gut crosstalk pathways play vital roles in the pathogenesis and progression of oral diseases, such as periodontitis, and gut diseases, such as inflammatory bowel disease (IBD). Focusing on periodontitis and IBD as representative conditions, this review summarizes current understanding of the oral-gut crosstalk and underlying mechanisms. Among diverse interactions, we emphasize BEVs as effective trans-barrier mediators and their therapeutic potentials during oral-gut crosstalk. Beneficial BEVs, notably those from <i>Akkermansia muciniphila</i> (<i>Akk</i>), exert various probiotic roles, including modulating microbial homeostasis, promoting tissue repair and alleviating inflammation, thereby shedding light on the prevention and treatment of oral and gut diseases, even systemic disorders.