Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
Hepatology. 2021 Nov;74(5):2670-2683. doi: 10.1002/hep.32017. Epub 2021 Aug 26.
Automated chyme reinfusion (CR) in patients with intestinal failure (IF) and a temporary double enterostomy (TDE) restores intestinal function and protects against liver injury, but the mechanisms are incompletely understood. The aim was to investigate whether the beneficial effects of CR relate to functional recovery of enterohepatic signaling through the bile salt-FGF19 axis.
Blood samples were collected from 12 patients, 3 days before, at start, and 1, 3, 5, and 7 weeks after CR initiation. Plasma FGF19, total bile salts (TBS), 7-α-hydroxy-4-cholesten-3-one (C4; a marker of bile salt synthesis), citrulline (CIT), bile salt composition, liver tests, and nutritional risk indices were determined. Paired small bowel biopsies prior to CR and after 21 days were taken, and genes related to bile salt homeostasis and enterocyte function were assessed. CR induced an increase in plasma FGF19 and decreased C4 levels, indicating restored regulation of bile salt synthesis through endocrine FGF19 action. TBS remained unaltered during CR. Intestinal farnesoid X receptor was up-regulated after 21 days of CR. Secondary and deconjugated bile salt fractions were increased after CR, reflecting restored microbial metabolism of host bile salts. Furthermore, CIT and albumin levels gradually rose after CR, while abnormal serum liver tests normalized after CR, indicating restored intestinal function, improved nutritional status, and amelioration of liver injury. CR increased gene transcripts related to enterocyte number, carbohydrate handling, and bile salt homeostasis. Finally, the reciprocal FGF19/C4 response after 7 days predicted the plasma CIT time course.
CR in patients with IF-TDE restored bile salt-FGF19 signaling and improved gut-liver function. Beneficial effects of CR are partly mediated by recovery of the bile salt-FGF19 axis and subsequent homeostatic regulation of bile salt synthesis.
在患有肠衰竭（IF）和临时双肠造口术（TDE）的患者中进行自动回肠输注（CR）可恢复肠道功能并预防肝损伤，但作用机制尚不完全清楚。本研究旨在探讨 CR 是否通过胆汁盐-FGF19 轴对肠肝信号转导的功能恢复产生有益影响。
收集了 12 例患者的血液样本，分别在 CR 开始前 3 天、开始时以及开始后 1、3、5 和 7 周采集。测定血浆 FGF19、总胆汁盐（TBS）、7-α-羟基-4-胆甾烯-3-酮（C4；胆汁盐合成的标志物）、瓜氨酸（CIT）、胆汁盐组成、肝酶和营养风险指数。在 CR 前和 21 天后采集配对的小肠活检样本，并评估与胆汁盐动态平衡和肠细胞功能相关的基因。CR 诱导血浆 FGF19 增加和 C4 水平降低，表明通过内分泌 FGF19 作用恢复了胆汁盐合成的调节。CR 期间 TBS 保持不变。CR 21 天后肠法尼醇 X 受体上调。CR 后次级和去结合胆汁盐分数增加，反映了宿主胆汁盐的微生物代谢恢复。此外，CR 后 CIT 和白蛋白水平逐渐升高，而异常的血清肝酶在 CR 后恢复正常，表明肠道功能恢复、营养状况改善和肝损伤减轻。CR 增加了与肠细胞数量、碳水化合物处理和胆汁盐动态平衡相关的基因转录本。最后，7 天后的 FGF19/C4 反向反应预测了 CIT 的血浆时间过程。
IF-TDE 患者的 CR 恢复了胆汁盐-FGF19 信号转导，并改善了肠道-肝脏功能。CR 的有益作用部分是通过恢复胆汁盐-FGF19 轴和随后的胆汁盐合成的稳态调节来介导的。
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