We previously reported that oral inoculation of the oral commensal bacteria Fusobacterium nucleatum (F. nucleatum) induced periodontitis and disrupts the intestinal immune response. However, the effect of the intestinal microfloral balance, inflammation of the intestinal tract, and the mechanism of periodontitis induction by F. nucleatum was unknown. Therefore, in this study, we examined the mechanism of colitis caused by oral inoculation with F. nucleatum. Mice were orally inoculated with F. nucleatum 5 times a week for 3 weeks and sacrificed either at day 1 or day 30 after their last oral inoculation. Feces, large intestine and blood were collected and used for enterobacterial, immunological, and histological analyses. The number of Clostridium spp. in the intestinal microbiome and the amount of IgA antibodies in the feces were significantly reduced. F. nucleatum was detected in the feces and serum on day 1 and in the large intestine and serum on day 30 after the last oral inoculation. The number of M1 macrophages was significantly higher in the F. nucleatumchallenged group. The gene expression and protein productions of IL -1β and IL -18 were significantly higher in the large intestine at day 30. Additionally, the expression of NLRP3 and GSDMD were also significantly elevated on day 30. Caspase -1 showed an increasing trend in both gene expression and protein production. However, Caspase -11 was significantly increased at the protein level, which persisted until day 30. These results suggested that Caspase-11 contributed to the induction of inflammation in the large intestine after F. nucleatum inoculation.

No abstract

We have previously reported that oral inoculation with Fusobacterium nucleatum (F. nucleatum) caused horizontal bone resorption and increases the RANKL/OPG ratio.However, the mechanism of periodontitis induction by F. nucleatum was unknown. This study investigated how oral inoculation with F. nucleatum induced periodontitis. Mice were inoculated orally with F. nucleatum 5 times a week for 3 weeks. At day 1 or day 30 after the last oral inoculation, the animals were euthanized and subjected to histological and immunological analyses.Significant alveolar bone resorption with osteoclasts was observed in the F. nucleatum inoculation group. Inflammatory cytokines were significantly increased in gene and protein assay at day 30 after the last oral inoculation. Interestingly, F. nucleatum was detected in the serum at day 30 but not in the gingival tissue. These findings suggested that gingival inflammation might be induced via the bloodstream. Therefore, when Ca9 -22 cells were added serum from F. nucleatuminoculated mice, IL -1β was significantly observed, which was confirmed by gene and protein assays. These results suggested that F. nucleatum in blood played a central role in periodontitis caused by oral inoculation of F. nucleatum. In addition, systemic circulation of F. nucleatum was likely to contribute not only to periodontitis but also to the pathogenesis of remote organs.