Data_Sheet_2_In Silico Analysis Identifies Intestinal Transit as a Key Determinant of Systemic Bile Acid Metabolism.zip

Bile acids fulfill a variety of metabolic functions including regulation of glucose and lipid metabolism. Since changes of bile acid metabolism accompany obesity, Type 2 Diabetes Mellitus and bariatric surgery, there is great interest in their role in metabolic health. Here, we developed a mathematical model of systemic bile acid metabolism, and subsequently performed in silico analyses to gain quantitative insight into the factors determining plasma bile acid measurements. Intestinal transit was found to have a surprisingly central role in plasma bile acid appearance, as was evidenced by both the necessity of detailed intestinal transit functions for a physiological description of bile acid metabolism as well as the importance of the intestinal transit parameters in determining plasma measurements. The central role of intestinal transit is further highlighted by the dependency of the early phase of the dynamic response of plasma bile acids after a meal to intestinal propulsion.

胆汁酸具有多种代谢功能，包括调控糖脂代谢。鉴于胆汁酸代谢异常常伴随肥胖、2型糖尿病及减重代谢手术发生，学界对其在代谢健康中的作用高度关注。本研究构建了全身胆汁酸代谢的数学模型，随后开展计算机模拟（in silico）分析，对影响血浆胆汁酸检测结果的相关因素进行定量解析。研究发现，肠道转运在血浆胆汁酸的释放入血过程中具有出人意料的核心作用，这一结论得到两方面证据的支持：一是精准描述胆汁酸代谢的生理特征需要纳入详细的肠道转运功能模块，二是肠道转运参数对血浆胆汁酸检测结果的确定具有关键影响。餐后血浆胆汁酸动态响应的早期阶段依赖于肠道推进功能，这进一步凸显了肠道转运的核心作用。