Quantifying forms and functions of intestinal bile acid pools in mice.
Quantifying forms and functions of intestinal bile acid pools in mice.
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量化小鼠肠道胆汁酸库的形式和功能。
DOI：
10.1101/2024.02.16.580658
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Karpe
中科院分区：
文献类型：
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作者：
Sudo,Koichi;Delmas-Eliason,Amber;Soucy,Shannon;Barrack,KaitlynE;Liu,Jiabao;Balasubramanian,Akshaya;Shu,ChengyiJenny;James,Michael;Hegner,CourtneyL;Dionne,HenryD;Rodriguez-Palacios,Alexander;Krause,Henry;O'Toole,GeorgeA;Karpe
胆汁酸（BA）是胃肠道代谢物，在脂质吸收和细胞信号传导中发挥双重作用。 BA 在肝脏和远端小肠（即回肠）之间活跃循环，但复杂的 BA 池在回肠中被吸收并与体内肠细胞相互作用的动力学仍然不明确。通过对野生型小鼠中近 100 个 BA 物种以及缺乏回肠 BA 转运蛋白 Asbt/Slc10a2 的小鼠进行多位点采样，我们计算出禁食 C57BL/6J 小鼠的回肠 BA 池为 ∼0.3 μmoles/g。 Asbt 介导的运输占该池的 80%，并放大了大小，而被动吸收则解释了剩余的 20%，并产生了多样性。因此，缺乏 Asbt 的小鼠的回肠 BA 库比野生型对照小约 5 倍，富含通常在结肠中发现的次生 BA 物种，并在培养的回肠外植体中引发独特的转录反应。这项工作定量定义了小鼠回肠 BA 库，并揭示了 BA 代谢障碍如何影响肠道生理学。
Bile acids (BAs) are gastrointestinal metabolites that serve dual functions in lipid absorption and cell signaling. BAs circulate actively between the liver and distal small intestine (i.e., ileum), yet the dynamics through which complex BA pools are absorbed in the ileum and interact with intestinal cellsin vivoremain ill-defined. Through multi-site sampling of nearly 100 BA species in individual wild type mice, as well as mice lacking the ileal BA transporter, Asbt/Slc10a2, we calculate the ileal BA pool in fasting C57BL/6J mice to be ∼0.3 μmoles/g. Asbt-mediated transport accounts for ∼80% of this pool and amplifies size, whereas passive absorption explains the remaining ∼20%, and generates diversity. Accordingly, ileal BA pools in mice lacking Asbt are ∼5-fold smaller than in wild type controls, enriched in secondary BA species normally found in the colon, and elicit unique transcriptional responses in cultured ileal explants. This work quantitatively defines ileal BA pools in mice and reveals how BA dysmetabolism can impinge on intestinal physiology.