Multi-prospects of bacterial extracellular vesicles in immune modulation, inflammation regulation, and periodontitis treatment

Periodontitis is a chronic and multifactorial inflammatory oral disease that not only causes alveolar bone loss and tooth loosening but also amplifies systemic inflammation. Breakdown of periodontal host-microbe homeostasis creates dysbiotic microbial communities of keystone pathogens that trigger the host immune response creating a pro-inflammatory milieu in the periodontal region. Keystone pathogens damage the periodontal tissue and facilitate bacterial immune escape via direct infection in periodontal tissue or release of bacterial extracellular vesicles (EVs) and other virulence factors such as lipopolysaccharide (LPS) and endotoxins. Bacterial EVs are ̴ 100 nm diameter nanovesicles that carry LPS, endotoxins, catalytic enzymes, and bacterial nucleic acids and can easily internalize in host cells. Keystone pathogen EVs have been reported to disrupt the survival and function of various cells in the periodontal region. In contrast, probiotic EVs have been reported to alleviate the progression of various inflammatory diseases including colitis and atopic dermatitis. Based on these facts, this review aimed to discuss the pathogenic bacterial EVs as possible targets and probiotic EVs as nano-drugs or nanocarriers for immune modulation, inflammation regulation, and periodontitis treatment in clinics. We also elaborated challenges and prospects of the development of bacterial EVs-based diagnostic and therapeutic approaches for periodontitis.