在肠道微生物群的最新进展中,肝脏孕妇X受体的代谢物调节
Tong Lin1, Yang Chen2, Linquan Liu3
1Department of Pharmacy, Fuyong People's Hospital of Baoan District, Shenzhen, China.
Frontiers in immunology
|December 10, 2025
概括
肠道微生物群通过直接连接体结合和表观遗传变化调节孕前X受体 (PXR),影响药物代谢和肝脏健康. 这种微生物群-PXR轴为代谢性肝脏疾病提供治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 孕妇X受体 (PXR) 是一个核受体,调节异生菌的新陈代谢和排毒.
- PXR的联结域 (LBD) 识别了多种分子,影响了药物反应和毒性的个体间变异性.
- 肠肝轴和微生物群代谢物越来越被认为是肝功能的调节者,包括PXR信号传递.
研究的目的:
- 阐明肠道微生物群代谢物调节肝脏PXR的双重机制.
- 调查直接体受体相互作用和表观遗传重编程在PXR激活中的作用.
- 探索微生物群-PXR轴对肝脏平衡,药物反应和疾病的影响.
主要方法:
- 对联体受体相互作用的分析,包括键和构造变化.
- 对表观遗传修饰的研究,如基因素乙化和SCFA的HDAC抑制.
- 评估基因表达变化 (例如,CYP3A4,ABCB1) 和炎症途径 (NF-κB).
主要成果:
- 微生物群的代谢物,如胆汁酸和IPA,直接与PXR-LBD结合,对CYP3A4/ABCB1进行上调和调节炎症.
- 短链脂肪酸 (SCFA) 在表观遗传上通过基因组乙化增强PXR转录,而不是直接结合于连接体.
- 失调的PXR信号与胆酸不平衡,线粒体功能障碍和化学抵抗有关.
结论:
- 肠道微生物群通过直接和表观遗传途径对PXR活性产生关键影响.
- 微生物群-PXR轴是药物反应异质性的关键因素,也是治疗肝脏疾病和癌症的潜在目标.
- 针对微生物群-PXR轴的干预措施,如益生菌或PXR调节剂,显示出治疗前景.
相关概念视频
Transducer Mechanism: Nuclear Receptors
2.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
2.3K
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
248
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
248
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug
192
In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
192
Hepatic Drug Excretion: Influencing Factors
504
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
504
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion
159
Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
159
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
169
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
169


