Data_Sheet_1_In Silico Analysis Identifies Intestinal Transit as a Key Determinant of Systemic Bile Acid Metabolism.pdf

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(bile acids)具备多种代谢功能，涵盖葡萄糖与脂质代谢的调控。鉴于胆汁酸代谢改变常伴随肥胖、2型糖尿病(Type 2 Diabetes Mellitus)及减重手术(bariatric surgery)的发生，学界对其在代谢健康中的作用抱有极高的研究热情。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，以定量解析影响血浆胆汁酸检测结果的各类因素。研究发现，肠道转运(intestinal transit)对血浆胆汁酸的释放入血具有出人意料的核心作用，这一结论可从两方面得到佐证：其一，若要对胆汁酸代谢进行生理学层面的精准描述，必须纳入精细化的肠道转运功能模块；其二，肠道转运参数对血浆胆汁酸检测结果的影响至关重要。餐后血浆胆汁酸动态响应的早期阶段依赖于肠道推进(intestinal propulsion)，这进一步凸显了肠道转运的核心地位。