Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Nantong Stomatological Hospital, Affiliated Nantong Stomatological Hospital of Nantong University, Nantong, China.
Front Cell Infect Microbiol. 2024 May 21;14:1413787. doi: 10.3389/fcimb.2024.1413787. eCollection 2024.
Trimethylamine-N-oxide (TMAO) is produced by hepatic flavin-containing monooxygenase 3 (FMO3) from trimethylamine (TMA). High TMAO level is a biomarker of cardiovascular diseases and metabolic disorders, and it also affects periodontitis through interactions with the gastrointestinal microbiome. While recent findings indicate that periodontitis may alter systemic TMAO levels, the specific mechanisms linking these changes and particular oral pathogens require further clarification.
In this study, we established a C57BL/6J male mouse model by orally administering (, ), (, ), (, ) and PBS was used as a control. We conducted LC-MS/MS analysis to quantify the concentrations of TMAO and its precursors in the plasma and cecal contents of mice. The diversity and composition of the gut microbiome were analyzed using 16S rRNA sequencing. TMAO-related lipid metabolism and enzymes in the intestines and liver were assessed by qPCR and ELISA methods. We further explored the effect of on FMO3 expression and lipid molecules in HepG2 cells by stimulating the cells with -LPS .
The three oral pathogenic bacteria were orally administered to the mice for 5 weeks. The group showed a marked increase in plasma TMAO, betaine, and creatinine levels, whereas no significant differences were observed in the gut TMAO level among the four groups. Further analysis showed similar diversity and composition in the gut microbiomes of both the and groups, which were different from the and control groups. The profiles of TMA-TMAO pathway-related genera and gut enzymes were not significantly different among all groups. The group showed significantly higher liver FMO3 levels and elevated lipid factors (IL-6, TG, TC, and NEFA) in contrast to the other groups. experiments confirmed that stimulation of HepG2 cells with -LPS upregulated the expression of FMO3 and increased the lipid factors TC, TG, and IL-6.
This study conclusively demonstrates that , compared to and , plays a critical role in elevating plasma TMAO levels and significantly influences the TMA-TMAO pathway, primarily by modulating the expression of hepatic FMO3 and directly impacting hepatic lipid metabolism.
三甲胺-N-氧化物（TMAO）是由肝脏黄素单加氧酶 3（FMO3）从三甲胺（TMA）产生的。高水平的 TMAO 是心血管疾病和代谢紊乱的生物标志物，它还通过与胃肠道微生物组的相互作用影响牙周炎。虽然最近的研究结果表明牙周炎可能改变全身 TMAO 水平，但连接这些变化和特定口腔病原体的具体机制仍需进一步阐明。
本研究通过口服给予 C57BL/6J 雄性小鼠 （ ， ）、 （ ， ）、 （ ， ）和 PBS 作为对照，建立了一个模型。我们通过 LC-MS/MS 分析定量检测了血浆和盲肠内容物中小鼠 TMAO 及其前体的浓度。通过 16S rRNA 测序分析肠道微生物组的多样性和组成。通过 qPCR 和 ELISA 方法评估 TMAO 相关的肠道和肝脏内脂质代谢和酶。我们还通过刺激 HepG2 细胞用 -LPS 来进一步探索 对 FMO3 表达和脂质分子的影响。
三种口腔致病菌被口服给予小鼠 5 周。组显示血浆 TMAO、甜菜碱和肌酐水平显著升高，而四组之间肠道 TMAO 水平没有显著差异。进一步分析显示，组和 组的肠道微生物组具有相似的多样性和组成，与组和对照组不同。TMA-TMAO 途径相关属和肠道酶的图谱在所有组之间没有显著差异。组的肝 FMO3 水平显著升高，与其他组相比，脂质因子（IL-6、TG、TC 和 NEFA）升高。实验证实，用 -LPS 刺激 HepG2 细胞可上调 FMO3 的表达并增加脂质因子 TC、TG 和 IL-6。
本研究明确表明，与 和 相比，在升高血浆 TMAO 水平方面发挥着关键作用，并且主要通过调节肝 FMO3 的表达显著影响 TMA-TMAO 途径，直接影响肝内脂质代谢。
