Probiotic-mediated therapy has sparked significant interests in various disease treatments due to its ability to eliminate harmful bacteria and regulate the host immune system (Tan et al., 2020, Gulnaz et al., 2024). Probiotics are beneficial microorganisms that play a role in maintaining a balanced and dynamic microbiota (Vuotto et al., 2014, Gao et al., 2018, Wang et al., 2023). Recent studies and emerging evidence consistently demonstrate the potential of the microorganisms to modulate bone remodeling (Lyu et al., 2023). Studies have demonstrated that specific probiotic strains can increase bone density (Morato-Martínez et al., 2020) and improves calcium absorption (EI-Gawad et al., 2009). Furthermore, pre-clinical studies highlight the anti-inflammatory properties of probiotics, demonstrating their ability to mitigate bone loss in models of ovariectomy (Ohlsson et al., 2014) and rheumatoid arthritis(Pan et al., 2019). These findings are particularly relevant to orthodontics, where controlled bone remodeling is essential for successful tooth movement.

Orthodontic treatment achieves tooth movement through bone remodeling involving alveolar bone resorption and formation (Zhang et al., 2024), and this process often requires a lengthy treatment duration. Enhancing the speed of bone reconstruction and optimizing the balance of this process are crucial for achieving accelerated orthodontic tooth movement (OTM) and shortening treatment time. Current methods for accelerating OTM, such as periodontal ligament distraction, low-intensity pulsed ultrasound, and piezopuncture, can be invasive and present challenges. Strengthening the potential of probiotics to modulate bone remodeling could offer a safer, non-invasive alternative.

While probiotics are often regarded for their ability to reduce harmful bacteria, their role in orthodontic treatment remains inconclusive. The use of probiotics during fixed orthodontic treatment has been demonstrated to reduce S. mutans and Lactobacillus levels in the saliva (Alp & Baka, 2018). However, a research indicates that probiotic supplementation, despite its potential benefits, did not significantly affect the development of inflammation in gingiva and decalcification in enamel (Hadj-Hamou et al., 2020). While previous research has focused on inhibiting harmful bacteria, the role of oral immunomodulation by specific microbial in accelerating tooth movement is not well understood. The interaction between microbial and biomechanical signals on periodontal cells and tissues remains understood (Schröder et al., 2021).

Modulating immune response has been recognized as one of the key mechanisms underlying probiotic action. The immune system recognizes microorganisms as foreign bodies, triggering large amounts of inflammatory cells to generate innate and adaptive responses(Cunningham-Rundles et al., 2000; Hashemi et al., 2023). Immunomodulatory effect is particularly important in OTM, where biomechanical forces applied to teeth trigger a complex inflammatory response in periodontal tissues (Gruber, 2019). This response involves immune cells that release inflammatory mediators, matrix-degrading enzymes, and osteoclast-activating molecules, that all important for bone remodeling. Particularly, macrophages have been exerts crucial roles in alveolar bone remodeling (Wang et al., 2022) and root resorption (He et al., 2015, Fang et al., 2022) during OTM. Immune cells would directly interact with bone cells, suggesting a potential avenue for probiotics to influence bone remodeling during orthodontic treatment.

A large amount of evidence suggests crucial links among microorganisms, host immune response, and bone remodeling, and the precise mechanisms remain to be fully elucidated. In our study, we aims to explore how microorganisms can accelerate tooth movement, investigate the immunomodulation mechanism by which probiotics enhance OTM through macrophages. Potential probiotic candidates have been identified through 16S rRNA gene sequencing in a mouse model of OTM. To investigate the osteoimmunomodulatory impact, primary periodontal ligament cells (PDLCs) were obtained from mouse periodontal ligaments and cultured with or without conditioned media (CM) derived from macrophages post-incubation with microtia. The results demonstrated that Enterococcus faecalis (E. faecalis) increased the number of M1-polarized macrophages, and a decreased osteogenic level in PDLCs treated with CM E. faecalis group. Moreover, E. faecalis increased the distance in antibiotic mixture (ABX) treated mice during OTM model. Ultimately, this research endeavors to explore novel immunomodulatory mechanisms by which microorganisms can accelerate OTM, paving the way for innovative therapeutic strategies in orthodontic field. The outcomes of this research include shortened orthodontic treatment durations with minimal interventions, offering pioneering advancements in orthodontic treatment.