Porphyromonas gingivalis Promotes 4-Nitroquinoline-1-Oxide-Induced Oral Carcinogenesis With an Alteration of Fatty Acid Metabolism

Abstract

Microbiota has been widely considered to play a critical role in human carcinogenesis. Human papilloma virus, hepatitis B and C virus, and <i>Helicobacter pylori</i> are implicated in the pathogenesis of cancer of uterine cervix, liver, and stomach, respectively. However, whether <i>Porphyromonas gingivalis (P. gingivalis)</i>, a common Gram negative oral bacteria, is associated with oral carcinogenesis still remains unclear and its underlying mechanism needs to be addressed. Here, we established a combined experimental system of 4NQO-induced oral carcinoma model and chronic periodontitis model and investigated the effects of <i>P. gingivalis</i> infection on oral carcinogenesis and fatty acid metabolism during oral carcinogenesis. The data showed that in this animal model, <i>P. gingivalis</i> infection induced mice periodontitis, increased the tongue lesion size and multiplicity of each mouse and promoted oral cancer development. <i>P. gingivalis</i> treatment significantly increased the level of free fatty acids and altered the fatty acid profile in tongue tissues and the serum of mice. And <i>P. gingivalis</i> induced the formation of fatty liver of the mice. Besides, immunohistochemical analysis and qRT-PCR showed that the expression of fatty-acid synthase and acetyl-CoA carboxylase 1 were increased in the tongue and liver tissues of 4NQO-treated mice infected with <i>P. gingivalis</i>. These results showed that <i>P. gingivalis</i> promoted oral carcinogenesis and aggravated disturbance of fatty acid metabolism, indicating a close association among <i>P. gingivalis</i>, lipid metabolic and oral carcinogenesis.