THU0066 DOES PORPHYROMONAS GINGIVALLIS MODULATE GUT MICROBIOME RESULTING IN AGGRAVATION OF DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS?
Authors: K. Kitamura, K. Terato, R. Fukai, K. Katayama, T. Waritani, H. Shionoya
Journal: Annals of the Rheumatic Diseases (2020)

Background: Oral Porphyromonas gingivalis (Pg) infection in rheumatoid arthritis (RA) model revealed aggravation of arthritis, dysbiosis and higher serum LPS (1). We reported that IgA/IgG antibody against Pg-LPS ratio among the patients with RA related to disease marker levels and disease activities (2). However, there are still few reports related to Gut-Oral axis. Objectives: Firstly, how total intestinal bacteria, well-known 5 species of gut bacteria behave in relation to disease activities and markers. Secondly, how infection by Pg aggravate RA in relation to microflora, disease activities and markers. Methods: Eighty-seven RA patients with inadequate response to conventional synthetic DMARDs were evaluated. Age: 68.1±8.7 years, female (%): 79.3, disease duration: 136±91 months, DAS28-ESR: 4.68±0.98. Fecal bacteria numbers of total bacteria, Bifidobacterium, Lactobacillus, E. coli, Bacteroides and Staphylococcus were determined by PCR analysis. Fecal and serum LPS levels were measured by LAL assay. Serum endotoxin neutralizing activity (ENC) was determined along with RA disease activity and markers measurement. Infection of Pg was proofed by IgG and IgA anti-LPS antibody measurement. The statistical relationships between variables were analyzed by Spearman’s non-parametric rank correlation analysis and expressed as Spearman’s rank correlation coefficient “ρ”. Results: At first, we could neglect background effects as duration, methotrexate dose for measuring total or each bacterial number (data not shown). As shown in Figure 1, total bacteria only showed positive correlation with IL-6 levels (ρ= 0.230, p = 0.034), however inversely correlated with disease activities such as pVAS (ρ= -0.223, p = 0.038) and Pain VAS (ρ= -0.260, p = 0.015). While no significant relationship was observed between the numbers of each of 5 species of bacteria and the disease activities and makers except Bifidobacterium. In contrast, LPS-related markers showed positive correlation with disease activities and markers. Among LPS-related biomarker values, serum LBP levels mainly correlated with most of RA biomarker-ESR (ρ= 0.497, p &lt;0.0001), CRP (ρ= 0.697, p &lt;0.0001), MMP3 (ρ= 0.546, p &lt;0.0001) and so on. Fecal LPS level was shown significant positive correlation with disease activities, however almost no correlation was observed in serum LPS level. IgA anti-LPS antibody levels to Pg, resulted in inverse correlation with total bacteria (ρ= -0.441, p&lt;0.0001), Lactobacillus (ρ= -0.224, p=0.037), Bacteroides (ρ = -0.200, p = 0.064) and E. coli (ρ= -0.260, p = 0.015), moreover, positive correlation with serum LPS (ρ= 0.284, p = 0.008) and LBP (ρ= 0.247, p = 0.021) and inverse correlation with ENC (ρ = -0.321, p = 0.002) were found. On the other hand, IgG anti-Pg-LPS antibody levels which reflect systemic infection, inversely correlated SDAI (ρ = -0.308, p = 0.004), PainVAS (ρ = -0.433, p &lt; 0.0001), and so on. Conclusion: Serum LBP highly associated with RA activity and markers, which suggests bacterial LPS as roles in triggering and perpetuating disease activity in RA. In contrast, IgA anti-Pg-LPS, IgG anti-Pg-LPS antibody reflecting infection of Pg, negatively associated with intestinal total bacteria (ρ=-0.4405, p&lt;0.0001), RA disease activities, respectively. These results may show a possible oral -gut relationship resulting in aggravation of disease activity in RA. Disclosure of interest: None declared References: [1]Sato K, Takahashi N, Kato T et al. Aggravation of collagen induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system. Sci Rep 2017; 7:6955. [2]Kuniaki Terato, Takaki Waritani, Richio Fukai et al. Contribution of bacterial pathogens to evoking serological disease markers and aggravating disease activity in rheumatoid arthritis. PloS One. 2018;13(2): e0190588. Disclosure of Interests: None declared