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

## TL;DR

This review explores how oral and gut microbes interact, focusing on bacterial extracellular vesicles as potential treatments for diseases like periodontitis and IBD.

## Contribution

Highlights the therapeutic potential of bacterial extracellular vesicles, especially from Akkermansia muciniphila, in oral–gut crosstalk.

## Key findings

- Oral–gut crosstalk involves bacterial translocation and immune signaling linked to disease progression.
- Bacterial extracellular vesicles (BEVs) act as mediators in intermucosal communication and disease modulation.
- Akkermansia muciniphila-derived BEVs show probiotic effects, including inflammation reduction and tissue repair.

## Abstract

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 Akkermansia muciniphila (Akk), 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.