Extensive bowel resection results in short bowel syndrome. Absence of the ileocecal valve and length of remaining bowel are important prognostic factors. Such patients require total parenteral nutrition for survival, which has significant side effects, thus understanding mechanisms driving total parenteral nutrition-associated complications in short bowel syndrome is a major research focus. We hypothesized that we could develop an ambulatory total parenteral nutrition-short bowel syndrome piglet model recapitulating human short bowel syndrome for advanced research. Fourteen neonatal pigs received duodenal, jugular catheters, and a jacket with a miniaturized pump. Animals were randomly allocated to enteral nutrition (n = 5), total parenteral nutrition only (n = 5) or total parenteral nutrition with 75% small bowel, ileocecal valve resection, and ileo-colonic anastomosis (n = 4). Blood, liver, and gut were analyzed. Animals underwent successful bowel resection and anastomosis. Increased bilirubin was noted in short bowel syndrome and total parenteral nutrition. Mean conjugated bilirubin (mg/dL)±SE was 0.036 ± 0.004 for enteral nutrition (P = 0.03), 1.29 ± 0.613 for total parenteral nutrition (P = 0.01), and 3.89 ± 0.51 for short bowel syndrome (P = 0.000064). Linear gut density was reduced in short bowel syndrome and total parenteral nutrition vs. enteral nutrition. The mean linear gut density (g/cm)±SE for distal gut was 0.30 ± 0.02 for enteral nutrition (P = 0.0005); 0.16 ± 0.01 for total parenteral nutrition (P = 0.01), and 0.11 ± 0.008 for short bowel syndrome (P = 0.0001). We noted gut adaptation in short bowel syndrome (P = 0.015) with significant reduction in gut FXR, gut FGF19, and enhanced hepatic CyP7A1 expression in short bowel syndrome and total parenteral nutrition (P < 0.05). We successfully created an ambulatory total parenteral nutrition-short bowel syndrome model with distal small bowel and ileocecal valve resection recapitulating human short bowel syndrome. Our model validated total parenteral nutrition-related hyperbilirubinemia and gut changes, as noted in human short bowel syndrome. This model holds great potential for future innovative research and clinical applications.

Impact statement

Short bowel syndrome is associated with significant comorbidities and mortality. This study is important as unlike current systems, it provides a validated piglet model which mirrors anatomical, histological, and serological characteristics observed in human SBS. This model can be used to advance knowledge into mechanistic pathways and therapeutic modalities to improve outcomes for SBS patients. This study is novel in that in addition to significant reduction in the remnant bowel and noted liver disease, we also developed a method to emulate ileocecal valve resection and described gut adaptive responses which has important clinical implications in humans.

中文翻译：

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回结肠吻合术的短肠综合征动态仔猪模型的开发和验证。

广泛的肠切除会导致短肠综合征。回盲瓣的缺失和剩余肠的长度是重要的预后因素。此类患者需要全肠外营养才能生存，这具有显着的副作用，因此了解驱动短肠综合征全肠外营养相关并发症的机制是一个主要研究重点。我们假设我们可以开发一种动态全肠外营养-短肠综合征仔猪模型，以重现人类短肠综合征，以供高级研究使用。十四只新生猪接受了十二指肠导管、颈静脉导管和带有微型泵的夹克。动物被随机分配至肠内营养（ n = 5）、仅全肠外营养（ n = 5）或全肠外营养加75%小肠、回盲瓣切除和回结肠吻合术（ n = 4）。分析了血液、肝脏和肠道。动物成功进行了肠切除和吻合。短肠综合征和全肠外营养中胆红素增加。肠内营养的平均结合胆红素 (mg/dL)±SE 为 0.036 ± 0.004 ( P = 0.03)，全肠外营养为 1.29 ± 0.613 ( P = 0.01)，短肠综合征为 3.89 ± 0.51 ( P = 0.000064)。与肠内营养相比，短肠综合征和全肠外营养的线性肠道密度降低。肠内营养的远端肠道平均线性肠道密度 (g/cm)±SE 为 0.30 ± 0.02 ( P = 0.0005)；全肠外营养为 0.16 ± 0.01（ P = 0.01），短肠综合征为 0.11 ± 0.008（ P = 0.0001）。我们注意到短肠综合征的肠道适应（ P = 0。015），在短肠综合征和全肠外营养中，肠道 FXR、肠道 FGF19 显着降低，肝脏 CyP7A1 表达增强（ P < 0.05）。我们成功创建了一个动态全肠外营养-短肠综合征模型，其中远端小肠和回盲瓣切除术再现了人类短肠综合征。我们的模型验证了全肠外营养相关的高胆红素血症和肠道变化，如人类短肠综合征所示。该模型对于未来的创新研究和临床应用具有巨大的潜力。

 影响报告

短肠综合征与显着的合并症和死亡率相关。这项研究很重要，因为与当前的系统不同，它提供了一个经过验证的仔猪模型，反映了在人类 SBS 中观察到的解剖学、组织学和血清学特征。该模型可用于推进对机制途径和治疗方式的了解，以改善 SBS 患者的预后。这项研究的新颖之处在于，除了显着减少残余肠道和明显的肝脏疾病外，我们还开发了一种模拟回盲瓣切除术的方法，并描述了肠道适应性反应，这对人类具有重要的临床意义。