Yao Chao, Lan Dongmei, Li Xue, Wang Yan, Qi Shengcai, Liu Yuehua
Department of Prothodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China; Medical College, Anhui University of Science and Technology, Huainan, China.
Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China; Department of Preventive Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, China.
Microbes Infect. 2023 Jan-Feb;25(1-2):105040. doi: 10.1016/j.micinf.2022.105040. Epub 2022 Aug 18.
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.
非酒精性脂肪性肝病（NAFLD）是一种代谢性肝病，最终可导致肝硬化和肝细胞癌。牙龈卟啉单胞菌（P.g）是引起牙周病的主要病原体，参与NAFLD的发展。我们研究的目的是进一步研究P.g在NAFLD中的直接作用及其潜在的分子机制。建立了口服P.g的动物模型，并评估了该模型中的肝功能和病理情况。分析了肠道微生物群和代谢产物。此外，评估了脾脏和肝脏中Th17/Treg的平衡。在我们的研究中，所有口服P.g的小鼠均出现了NAFLD。口服P.g后，肠道微生物群和代谢产物发生了改变。口服P.g后，在小鼠肝脏中观察到P.g和铁死亡。此外，在体外肝细胞中也观察到了铁死亡，但铁死亡抑制剂可使其逆转。另外，P.g在体内引发了肝脏和脾脏中Th17/Treg比例的失衡。这些发现表明，口服P.g可直接诱导小鼠发生NAFLD，这可能依赖于通过微生物代谢紊乱诱导的Th17/Treg失衡而发生的肝细胞铁死亡。因此，改善牙周环境是预防NAFLD的一种新的治疗策略。
