Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase

Abstract

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 (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad 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 comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad 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, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad 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.

Sodium houttuyfonate derived fromHouttuynia cordataThunb improves intestinal malfunctionviamaintaining gut microflora stability inCandida albicansovergrowth aggravated ulcerative colitis

“…Histological activity index grading is assessed by epithelium (0, normal morphology; 1, minimal loss of goblet cells; 2, extensive loss of goblet cells; 3, loss of crypts; 4, loss of crypts in large areas) and infiltration (0, no infiltrate; 1, infiltrate around the crypt base; 2, infiltrate in the muscularis mucosa; 3, extensive infiltrate in the muscularis mucosa with edema; 4, infiltration in the submucosa). 37…”

Association between Porphyromonas Gingivalis and systemic diseases: Focus on T cells-mediated adaptive immunity

“…found that P. gingivalis exacerbated the severity of UC, in part through Porphyromonas gingivalis peptidylarginine deiminase (PPAD). The main mechanisms are stimulation of Th17 numbers and IL-17 production, and reduction of Treg numbers and IL-10 production ( Zhao et al., 2021 ). According to a recent study, P. gingivalis modifies the gut microbiota, which eventually stimulates intestinal IL-9+CD4+T cells and inflammation ( Sohn et al., 2022 ).…”

The oral microbiome in autoimmune diseases: friend or foe?

“…Klebsiella strains isolated from the salivary microbiota with multidrug resistance were capable of colonizing the colon and increasing the numbers of proinflammatory TH1 cells, which subsequently aggravated the progression of IBD [ 104 ]. In addition, PADs, an enzyme or virulence factor specific to P. gingivalis , promotes the production of Th17 cells and IL-17, causing aggravation of UC [ 144 ]. It has been demonstrated that P. gingivalis dramatically increases the severity of colitis by breaking down TJPs to increase the permeability of the intestinal epithelium [ 145 ].…”