Mechanistic inference of the metabolic rates underlying $$^{13}$$C breath test curves
Mechanistic inference of the metabolic rates underlying $$^{13}$$C breath test curves
复制标题
$$^{13}$$C 呼吸测试曲线基础代谢率的机械推断
DOI：
10.1007/s10928-023-09847-x
复制
发表时间：
2023
影响因子：
2.5
通讯作者：
Morrison, Douglas J.
中科院分区：
文献类型：
--
作者：
Brouwer, Andrew F.;Lee, Gwenyth O.;Schillinger, Robert J.;Edwards, Christine A.;Wyk, Hannah Van;Yazbeck, Roger;Morrison, Douglas J.
碳稳定同位素呼吸测试为更好地了解健康和疾病中的胃肠道功能提供了新的机会。然而，通常不清楚如何从呼吸测试曲线中分离出有关胃肠道或代谢过程的信息，并且通常不知道经验曲线拟合的汇总统计数据与潜在的生物率之间的相关性如何。我们开发了一个框架，可用于对13c呼吸测试曲线的代谢率进行机制推断，并将其应用于20名健康成人的13c -蔗糖呼吸测试的初步研究。从蔗糖代谢的标准概念模型开始，我们分别使用代数和轮廓似然确定了模型的结构和实际可识别性，并利用这些结果开发了一个简化的、可识别的模型，作为伽马分布过程的函数；缓慢的，有速率限制的过程；一个标度术语与呼出的底物的比例相对于通过尿液被隔离或排泄的比例。我们演示了可识别的模型参数如何影响曲线动力学，以及这些参数如何与常用的呼吸测试汇总测量相关联。我们的工作更好地理解了潜在的生物过程如何影响13c呼吸测试曲线的不同方面，增强了这些13c呼吸测试的临床和研究潜力。图形抽象
Carbon stable isotope breath tests offer new opportunities to better understand gastrointestinal function in health and disease. However, it is often not clear how to isolate information about a gastrointestinal or metabolic process of interest from a breath test curve, and it is generally unknown how well summary statistics from empirical curve fitting correlate with underlying biological rates. We developed a framework that can be used to make mechanistic inference about the metabolic rates underlying a13C breath test curve, and we applied it to a pilot study of13C-sucrose breath test in 20 healthy adults. Starting from a standard conceptual model of sucrose metabolism, we determined the structural and practical identifiability of the model, using algebra and profile likelihoods, respectively, and we used these results to develop a reduced, identifiable model as a function of a gamma-distributed process; a slower, rate-limiting process; and a scaling term related to the fraction of the substrate that is exhaled as opposed to sequestered or excreted through urine. We demonstrated how the identifiable model parameters impacted curve dynamics and how these parameters correlated with commonly used breath test summary measures. Our work develops a better understanding of how the underlying biological processes impact different aspect of13C breath test curves, enhancing the clinical and research potential of these13C breath tests.Graphic abstract