Balanced oral pathogenic bacteria and probiotics promoted wound healing via maintaining mesenchymal stem cell homeostasis

OBJECTIVES: The homeostasis of oral pathogenic bacteria and probiotics plays a crucial role in maintaining the well-being and healthy status of human host. Our previous study confirmed that imbalanced oral microbiota could impair mesenchymal stem cell (MSC) proliferation capacity and delay wound healing. However, the effects of balanced oral pathogenic bacteria and probiotics on MSCs and wound healing are far from clear. Here, the balance of pathogenic bacteria Porphyromonas gingivalis and probiotics Lactobacillus reuteri extracts was used to investigate whether balanced oral microbiota modulate the physiological functions of MSCs and promote wound healing. METHODS: The effects of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts on gingival MSCs (GMSCs) were tested using the migration, alkaline phosphatase activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts in the wound of mice, the wounds were established in the mucosa of palate and were inoculated with bacteria every 2 days. RESULTS: We found that the balance between pathogenic bacteria and probiotics enhanced the migration, osteogenic differentiation, and cell proliferation of MSCs. Additionally, local inoculation of the mixture of L. reuteri and P. gingivalis promoted the process of wound healing in mice. Mechanistically, we found that LPS in P. gingivalis could activate NLRP3 inflammasome and inhibit function of MSCs, thereby accelerating MSC dysfunction and delaying wound healing. Furthermore, we also found that reuterin was the effective ingredient in L. reuteri which maintained the balance of pathogenic bacteria and probiotics by neutralizing LPS in P. gingivalis, thus inhibiting inflammation and promoting wound healing. CONCLUSIONS: This study revealed that the homeostasis of oral microbiomes played an indispensable role in maintaining oral heath, provided hopeful methods for the prevention and treatment of oral diseases, and had some referential value for other systemic diseases caused by dysfunction of microbiota and MSCs.