Tiny but mighty: Possible roles of bacterial extracellular vesicles in gut-liver crosstalk for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) with an increasing incidence is one of the leading causes for liver transplantation and cancer, whereas understandings on the onset and development of this disease are quite limited. Nowadays, gut microbial dysregulation has been proposed to play a critical role in the immune-metabolic disorders in NAFLD patients via gut-liver axis. Although definitive crosstalk between gut and liver has not been thoroughly depicted, the nanosized bacterial extracellular vesicles (bEVs) capable of transporting multiple kinds of molecules to distant organs of host in intact form via system circulation act as major mediators in host-bacterial interactions. A recent review has confirmed the associations between bEVs and NAFLD features such as insulin resistance and liver inflammation, whereas the mechanisms involved have not been elucidated. Considering that gut-liver crosstalk is the main pathway through which bEVs take part in NAFLD pathogenesis, we summarize the recent findings of bEVs in gut-liver crosstalk by modulating the reshape of gut microbial system, host intestinal barrier integrity, host immune responses and metabolic homeostasis, as well as the potential roles of bEVs in regulating NAFLD progression. Metabolites and cytokines from liver confer environmental stress to gut microbiota. Under the environmental stress, bacteria secrete extracellular vesicles (bEVs) to help survival. The secreted bEVs then mediate gut microbial remodelling and intestinal barrier dysfunction. Via impaired intestinal barrier, bEVs enter host circulation and generate direct crosstalk with cells in liver. image