High through-put sequencing analysis of changes in oral flora in rats before and after zoledronate administration


      The aim of this study was to compare the changes in the oral flora of Sprague-Dawley rats before intraperitoneal injection of zoledronic acid, 6 weeks and 12 weeks after injection. Clinically, some antibiotics effectively treat patients with medicine-related osteonecrosis of the jaws (MRONJ), but the effect of broad-spectrum antibiotics for osteomyelitis of the jaw is not obvious. We therefore speculated that MRONJ may have some dominant bacteria. We used 12 healthy rats for the experiment. One rat was used for haematoxylin and eosin staining, three were used for gene analysis, three for signal molecule research, and five for 16SrDNA high-pass sequencing to compare the changes of flora before intraperitoneal injection of zoledronic acid, and 6 and 12 weeks after injection once every three days. Alpha and beta analysis was used for sequencing data. Analysis of the flora showed that the alpha diversity of the bacteria of rats injected with zoledronic acid was significantly higher than it was before injection (p < 0.05). At the phylum level, Bacteroidetes at 6 and 12 weeks of injection were significantly higher than those before injection (p < 0.05). At the genus level, the proportions of Novophingobium, Dubosiella, Mannheimia, Prevotella, Brevundimonas, and Bacteroides were higher than they were before injection (p < 0.05). The proportions of Lactobacillus, Mannheimia, Brevundimonas, Bacteroides, Roseovarius, Salegentibacter, Marinobacter, and Granulicatella in rats injected for 12 weeks were higher than those before injection (p < 0.05). Zoledronic acid can change the structure of oral flora in SD rats, in which Bacteroides increased and Actinomycetes decreased.


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