<i>Fusobacterium nucleatum</i> Induces Gut Dysbiosis and Inflammasome and Promotes Colonic Inflammation

Abstract

We previously reported that oral inoculation of the oral commensal bacteria Fusobacterium nucleatum（F. nucleatum）induced periodontitis and disrupts the intestinal im mune 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. nucleatum-challenged 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.