Zhongguo quanke yixue (Jun 2024)
Effects of Irrigation of Porphyromonas Gingivalis on Colonic Mechanical and Immune Barriers in Type 2 Diabetic Mice
Abstract
Background Porphyromonas gingivalis (Pg.) is the main pathogen of periodontitis. Studies have found that Pg. can affect systemic diseases including type 2 diabetes mellitus (T2DM) through oral-intestinal pathway, but its specific mechanism remains unclear. Objective To explore whether Pg. has an effect on T2DM by changing intestinal mechanical and immune barriers. Methods A total of 24 among 40 SPF mice were randomly selected to construct T2DM models, among the successful models, 16 mice were selected to be divided into the model group (DM group, n=8) and model+Pg. group (PD group, n=8), and the other 16 mice were divided into the control group (N group, n=8) and Pg. group (n=8). After modeling, body mass and fasting plasma glucose (FPG) of mice were observed, and oral glucose tolerance test (OGTT) was performed at the 5th week, OGTT curve was plotted and the area under the curve (AUC) was calculated. Pg. group and PD group were gavaged with Pg. bacterial solution from the 7th week for 5 consecutive weeks. Lipopolysaccharide (LPS) was determined by enzyme-related immunosorbent assay (ELISA), colonic tight-junction protein and inflammatory factors were detected by real-time fluorescence quantitative PCR, and colonic tissue lesions were observed by hematoxylin-eosin (HE) staining. Pearson correlation or Spearman correlation analysis was used to investigate the relationship of FPG with colonic tight junction protein mRNA expression and serum LPS levels in mice. Results Body weight of DM group was higher than that of N group and Pg. group at 2nd to 6th weeks before irrigation (P<0.05), and body weight of PD group was higher than that of N group and body weight of PD group was higher than that of Pg. group at 3rd to 6th weeks before irrigation (P<0.05). The body weight of N group and Pg group was higher than that of DM group and PD group at 9th to 11th weeks, and the body weight of PD group was lower than that of DM group at 11th week (P<0.05). FPG in PD group was higher than that in the N and Pg. groups at 3rd to 6th weeks, and FPG in the DM group at 4th to 6th weeks was higher than that in N and Pg. groups. FPG of Pg. group was lower than that of the DM group and PD group at 7th to 11th weeks, PD group was higher than that of the N group, and PD group at week 10 and 11 was higher than the Pg. group (P<0.05). AUC in the DM group was higher than that in the N group and Pg. group, and PD group was higher than that in the N group, DM group and Pg. group (P<0.05). LPS of PD group was higher than that of N group and DM group (P<0.05). Tight junction protein 1 (ZO-1) in the PD group was lower than that in the N group, occludin in the DM group was lower than that in the N group, occludin in the PD group was lower than that in the N group, DM group and Pg. group (P<0.05). The interleukin (IL) -17A in the PD group was lower than that in the N group and Pg. group, and IL-10 in the N group was higher than that in the DM group and Pg. group (P<0.05). Tumor necrosis factor α in the PD group was higher than that in the N group, DM group and Pg. group (P<0.05). Toll-like receptor 4 in the Pg. group and PD group was higher than that in N group (P<0.05). Correlation analysis showed that FPG was positively correlated with LPS, and negatively correlated with occludin, ZO-1 (P<0.05). The pathological results showed connective tissue hyperplasia with focal lymphocyte infiltration in the lamina propria in the Pg. and DM groups, and the lamina propria with focal lymphocyte infiltration in the PD group. Conclusion Pg. may aggravate the glucose metabolism disorders of T2DM mice by disrupting the intestinal mechanical barrier and immune barrier leading to LPS entry into the bloodstream.
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