Lactiplantibacillus plantarum P101 Ameliorates TiO2 NP-Induced Bone Injury in Young Rats by Remodeling the Gut Microbiota and Inhibiting the Production of Pro-Inflammatory Cytokines.

Purpose: To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO₂ NPs), and explore the potential mechanism.

Methods: Four-week-old male rats were orally administration to TiO₂ NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.

Results: Our results showed that TiO₂ NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO₂ NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO₂ NPs.

Conclusion: This study showed that the mechanism by which P101 alleviates bone damage caused by TiO₂ NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response.