以生理学为基础的动力学 (PBK) 建模作为一种新的方法方法 (NAM) 用于预测肠道微生物代谢物的系统水平
Maja Stevanoska1, Jacob Folz1, Karsten Beekmann2
1Laboratory of Toxicology, Institute of Food, Nutrition and Health (IFNH), Department of Health Sciences and Technology, ETH Zürich, Switzerland.
Toxicology letters
|April 30, 2024
概括
新方法方法 (NAMs) 整合了体外和体内测试,以减少动物使用. 本综述检查了结合肠道微生物代谢的生理基动力学 (PBK) 模型,以改善化学风险评估.
科学领域:
- 毒理学和药理学 毒理学和药理学
- 计算生物学 计算生物学
- 微生物组研究 微生物组研究
背景情况:
- 化学风险评估需要动物试验的替代方案,推动新方法方法 (NAM) 的发展.
- 基于生理学的动力学 (PBK) 模型正在成为关键的NAM,但它们在毒性/药物动力学中的应用需要对肠道微生物代谢进行增强的建模.
- 肠道微生物组显著改变异生菌,影响宿主暴露和反应,但对这种影响的全面量化仍然是一个挑战.
研究的目的:
- 审查整合肠道微生物生物转换的基于生理的动力学 (PBK) 模型.
- 突出表现出ex vivo/in vitro方法对于量化微生物代谢常数的重要性.
- 评估这些综合模型在准确预测异生菌和代谢物度方面的潜力.
主要方法:
- 对现有的结合肠道微生物代谢的PBK模型的文献综述.
- 对测量微生物代谢动态的实验方法的ex vivo/in vitro分析.
- 评估了综合PBK模型成功预测体内条件的案例研究.
主要成果:
- 虽然将肠道微生物代谢纳入PBK模型的整合正在推进,但缺乏标准化.
- 不同的发酵技术产生可变的运动常数,使模型参数化复杂化.
- 具体的例子表明,使用集成PBK模型成功预测了系统代谢物度.
结论:
- 将肠道微生物代谢纳入PBK模型对于全面的化学风险评估至关重要.
- 需要标准化的ex vivo/in vitro方法来确保这些模型的可靠参数化.
- 进一步开发综合的PBK模型对减少和取代动物试验具有显著的前景.
相关概念视频
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