Oral Administration of P. Gingivalis and Alteration of Gut Microbiota

Objectives: Periodontitis has been implicated as a risk factor for various systemic diseases. However, the precise mechanisms by which periodontitis induces systemic disorders have not yet been clarified. Using a mouse model, after 10 administrations of Porphyromonas gingivalis (P. gingivalis) we have shown that swallowed oral bacteria elicit endotoxemia via change in gut microbiota, thereby inducing systemic inflammation and insulin resistance. However, additional effects of the oral administration of P. gingivalis are still unclear. Also the significance of the impact after a single administration of P. gingivalis has remained unclear. Therefore, using a single-administration mouse model, we analyzed the change in gut microbiota over time and the subsequent systemic dissemination of bacteria.
Methods: C57BL/6 mice were orally administered or sham-administered with P. gingivalis strain W83 once before being sacrificed at 3, 24 or 48hrs. The composition of gut microbiota was analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined using a Limulus amebocyte lysate test. Gene expressions in the intestine and amounts of P. gingivalis and other bacteria in the liver and the blood were evaluated by quantitative real-time PCR.
Results: A single administration of P. gingivalis significantly changed gut microbiota. Amounts of bacterial DNA in the liver tissue and serum endotoxin levels were statistically higher in the P. gingivalis-administered mice compared with the sham-administered mice. In the intestinal tissues, gene expressions of occludin and tjp-1, which are related to intestinal permeability, were down-regulated in the P. gingivalis-administered mice.
Conclusions: Just a one-time administration of P. gingivalis can significantly alter gut microbiota and increase intestinal permeability, thereby increasing serum endotoxin levels and the amount of bacteria in the liver.