Periodontitis induced by Porphyromonas gingivalis drives impaired glucose metabolism in mice

Abstract

Periodontitis has been demonstrated to be bidirectionally associated with diabetes and has been recognized as a complication of diabetes. As a periodontal pathogen, Porphyromonas gingivalis is a possible pathogen linking periodontal disease and systemic diseases. It has also been found to be involved in the occurrence and development of diabetes. In this study, 6-week-old male C57BL/6 mice were orally administered the P. gingivalis strain ATCC381 for 22 weeks. Histological analysis of the gingival tissue and quantified analysis of alveolar bone loss were performed to evaluate periodontal destruction. Body weight, fasting glucose, glucose tolerance test (GTT), and insulin tolerance test (ITT) were used to evaluate glucose metabolism disorder. We then analyzed the expression profiles of inflammatory cytokines and chemokines in gingival tissue, the liver, and adipose tissue, as well as in serum. The results showed that mice in the P. gingivalis-administered group developed apparent gingival inflammation and more alveolar bone loss compared to the control group. After 22 weeks of P. gingivalis infection, significant differences were observed at 30 and 60 min for the GTT and at 15 min for the ITT. P. gingivalis-administered mice showed an increase in the mRNA expression levels of the pro-inflammatory cytokines (TNF-α, IL-6, IL-17, and IL-23) and chemokines (CCL2, CCL8, and CXCL10) in the gingiva and serum. The expression levels of the glucose metabolism-related genes were also changed in the liver and adipose tissue. Our results indicate that oral administration of P. gingivalis can induce changes in the inflammatory cytokines and chemokines in the gingiva and blood, can lead to alveolar bone loss and to inflammatory changes in the liver and adipose tissues, and can promote glucose metabolism disorder in mice.

Association between periodontitis and the prevalence and prognosis of prediabetes: a population-based study

“…The level of insulin resistance was significantly elevated. Furthermore, Luan et al utilized P. gingivalis to establish an animal model [ 29 ]. They revealed that the levels of TNF-α and IL-6 were increased and the expression of PPARa, Irs1, and sitr1 was decreased, which suggested that glucose metabolism was dysregulated.…”

Developmental endothelial locus‐1 promotes osteogenic differentiation and alveolar bone regeneration in experimental periodontitis with type 2 diabetes mellitus

“…21 It is believed that periodontitis and diabetes are related in a bidirectional manner. 22,23 Treatment modalities for periodontitis with T2DM are being explored. It is realized that effectively promoting alveolar bone regeneration in the inflammation resolution stage may provide a new perspective on periodontitis with T2DM treatment.…”

“…Periodontitis is an inflammatory disease that leads to inflammatory bone loss around teeth 21 . It is believed that periodontitis and diabetes are related in a bidirectional manner 22,23 . Treatment modalities for periodontitis with T2DM are being explored.…”

Host insulin resistance caused by Porphyromonas gingivalis-review of recent progresses

“…Seyama et al, 2020 study found that outer membrane vesicles released by P. gingivalis attenuated Akt/glycogen synthase kinase-3b (GSK-3b) signaling in hepatic HepG2 cells, inducing insulin resistance and allowing insulin-induced reduction in hepatic glycogen synthesis, thereby maintaining high blood glucose levels (Seyama et al, 2020). Bhat et al, 2014 demonstrated that P.g-LPS stimulates insulin secretion from the pancreatic b-cell lineage MIN cells.P.g-LPS may be important in the development of b-cell compensation and insulin resistance in patients with periodontitis in prediabetes (Bhat et al, 2014).Tian, J et al an animal study showed that P. gingivalis periodontal infection significantly upregulated plasma branched-chain amino acid levels and exacerbated The plasma branched-chain amino acid biosynthetic pathway may provide a potential target for the link between periodontitis and T2DM (Kang et al, 2022).…”

“…P.g -LPS may be important in the development of b-cell compensation and insulin resistance in patients with periodontitis in prediabetes ( Bhat et al., 2014 ).Tian, J et al. an animal study showed that P. gingivalis periodontal infection significantly upregulated plasma branched-chain amino acid levels and exacerbated The plasma branched-chain amino acid biosynthetic pathway may provide a potential target for the link between periodontitis and T2DM ( Kang et al., 2022 ).…”