IDDF2024-ABS-0236 Impact of antibiotics-induced gut microbiota changes on bone regeneration in murine calvarial defects

<h3>Background</h3> Gut microbiota has been shown to be an important regulator of health and development. The intestinal flora can maintain the homeostasis of the host immune system, participate in the regulation of osteoclast and osteoblast activity, and affect the body’s bone remodeling. This study aims to elucidate the link between gut microbiota and bone healing in murine calvarial defects, focusing on the effect of antibiotic-induced gut microbiota dysbiosis. <h3>Methods</h3> The mice were pooled and then randomly into treatment groups. Those in the experimental group received a broad-spectrum antibiotic treatment (ampicillin, 1g/L; neomycin sulfate, 1g/L; vancomycin, 500mg/L) via their drinking water, while the control group did not. After a two-week period of antibiotic treatment, parameters such as cecum weight and volume, as well as the richness and diversity of gut microbiota, were assessed using 16S rRNA sequencing in both antibiotic-treated and untreated (control) mice. Subsequently, the mice were anaesthetized with isoflurane and underwent the induction of a singular critical-sized calvarial bone defect at the central region of the right parietal bone using a 1 mm burr drill. The bone volume/total volume (BV/TV%) was also analyzed at 2 and 4 weeks post-surgery in both groups. <h3>Results</h3> Antibiotic treatment in mice resulted in larger and heavier ceca (IDDF2024-ABS-0236 Figure 1 (A,B)). Decreased gut microbiota richness and diversity were observed after two weeks of antibiotic administration (IDDF2024-ABS-0236 Figure 1 (C,D)). From the micro-CT results, while no significant difference in bone healing was observed at the 2-week mark, antibiotics-treated mice exhibited significantly enhanced bone formation compared to controls at 4 weeks post-surgery (IDDF2024-ABS-0236 Figure 1 (E,F)). Histological analysis revealed collagen-rich osteoid mineralization, confirming pronounced bone formation in the antibiotics-treated group at 4 weeks (IDDF2024-ABS-0236 Figure 1 (G)). <h3>Conclusions</h3> Our study unveiled that alterations in gut microbiota diversity induced by antibiotics have the potential to enhance bone healing in murine calvarial defects. Further investigations are warranted to investigate the underlying mechanisms.