DOP026 Porphyromonas gingivalis secreted htpG disrupts TLR4/ PAPSS2-mediated mucin sulfation and aggravates ulcerative colitis
Authors: Wang A , Ding Y , Cao H 
Published: January 2025

Background

The role of the oral microbiota in the development of IBD and its association with disease severity has been established. However, the specific impact and mechanism of Porphyromonas gingivalis (P.g), a major pathogenic bacteria in the oral cavity, in exacerbating colitis remain unclear. Our objective is to investigate how P.g exacerbates ulcerative colitis.

Methods

Fecal samples were collected from patients with active ulcerative colitis and compared to those from healthy controls to assess the abundance of P.g. The impact of P.g on colitis and the colonic mucosal barrier was evaluated using a dextran sulfate sodium (DSS)-induced UC model in mice. Fecal and colonic mucosal tissue samples underwent 16S rRNA and transcriptome sequencing. Additionally, mass spectrometry analysis was conducted to further validate the role of bacterial supernatant proteins.

Results

The relative abundance of P.g in the feces of patients with UC was significantly higher compared to healthy individuals(P&lt;0.05). Furthermore, the abundance of P.g in the feces of patients with UC was positively correlated with markers reflecting the severity of UC (Mayo score, FC, ESR levels). In the DSS-induced colitis model, P.g exacerbated the severity of colitis, leading to a decrease in body weight and reduction in colon length. Moreover, P.g reduce the intestinal mucin sulfation and aggravate colitis. Mechanistically, P.g downregulates key molecules involved in mucin sulfation, including Papss2 and Slc35b3, the synthesis enzyme and the transferase of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), via the Toll-like Receptor 4 (TLR4). Additionally, mass spectrometry analysis indicated that the P.g HtpG protein exerts a pro-inflammatory effect.

Conclusion

Our study provides evidence that P.g can exacerbate colitis, potentially through the downregulation of MUC2 mucin sulfation by its secreted HtpG protein, which regulates PAPSS2 via TLR4.

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