Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Delta ppad) and a Delta ppad strain in which the PPAD gene was restored (com Delta ppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Delta ppad, or com Delta ppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and com Delta ppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Delta ppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Delta ppad, P. gingivalis, and com Delta ppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Delta ppad, or com Delta ppad with T lymphocytes in vitro and found that P. gingivalis and com Delta ppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.

Automated summary

Porphyromonas gingivalis exacerbates the severity of ulcerative colitis through its virulence factor PPAD, which affects immune cell numbers and interferes with cytokine production.