Abstract
Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that can eventually lead to liver cirrhosis and hepatocellular carcinoma. Porphyromonas gingivalis (P.g) is the main pathogen that causes periodontal disease, which participates in the development of NAFLD. The purpose of our study was to further study the direct role of P.g in NAFLD and the underlying molecular mechanism. An animal model of oral P.g administration was established, and liver function and pathology in this model were evaluated. The gut microbiome and metabolic products were analysed. Furthermore, the Th17/Treg balance in the spleen and liver was assessed. In our study, NAFLD was observed in all the mice that were orally administered P.g. The gut microbiome and metabolic products were altered after oral P.g administration. P.g and ferroptosis were observed in the livers of the mice after oral P.g administration. Additionally, ferroptosis was observed in hepatocytes in vitro, but it was reversed by ferroptosis inhibitors. In addition, P.g triggered an imbalance in the Th17/Treg ratio in the liver and spleen in vivo. These findings suggest that oral P.g administration directly induced NAFLD in mice, which may be dependent on the ferroptosis of liver cells that occurs through the Th17/Treg imbalance induced by disordered microbial metabolism. Therefore, improving the periodontal environment is a novel treatment strategy for preventing NAFLD.