Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, United States.
Nebraska Center for Biotechnology, University of Nebraska Lincoln, Lincoln, Nebraska, United States.
Am J Physiol Gastrointest Liver Physiol. 2024 Nov 1;327(5):G685-G696. doi: 10.1152/ajpgi.00151.2024. Epub 2024 Sep 3.
Congenital heart disease (CHD) is the most common birth defect, occurring in roughly 40,000 U.S. births annually. Malnutrition and feeding intolerance (FI) in CHD range from 30% to 42% and are associated with longer hospitalization and increased mortality. Cardiopulmonary bypass (CPB) required for surgical repair of CHD induces a systemic inflammatory response worsening intestinal dysbiosis and leading to intestinal epithelial barrier dysfunction (EBD), possibly contributing to postoperative FI. The objective of this study was to determine the relationship of postoperative FI with intestinal microbiome, short-chain fatty acids (SCFAs), and EBD in pediatric CHD after cardiac surgery. This was a prospective study of patients aged 0-15 years undergoing cardiac surgery with CPB. Samples were collected preoperatively and postoperatively to evaluate the gut microbiome, plasma EBD markers, short-chain fatty acids (SCFAs), and plasma cytokines. Clinical data were collected to calculate a FI score and evaluate patient status postoperatively. We enrolled 26 CPB patients and identified FI ( = 13). Patients with FI had unique microbial shifts with the reduced SCFA-producing organisms , , and . Patients who developed FI had associated elevations in the plasma EBD markers claudin-2 ( < 0.05), claudin-3 ( < 0.01), and fatty acid binding protein ( < 0.01). Patients with FI had reduced plasma and stool SCFAs. Mediation analysis showed the microbiome functional shift was associated with reductions in stool butyric and propionic acid in patients with FI. In conclusion, we provide novel evidence that intestinal dysbiosis, markers of EBD, and SCFA depletion are associated with FI. These data will help identify mechanisms and therapeutics to improve clinical outcomes following pediatric cardiac surgery. Feeding intolerance contributes to postoperative morbidity following pediatric cardiac surgery. The intestinal microbiome and milieu play a vital role in gut function. Short-chain fatty acids are gut and cardioprotective metabolites produced by commensal bacteria and help maintain appropriate barrier function. Depletion of these metabolites and barrier dysfunction contribute to postoperative feeding intolerance following cardiac surgery. Identifying mechanistic targets to improve the intestinal milieu with the goal of improved nutrition and clinical outcomes is critical.
先天性心脏病（CHD）是最常见的出生缺陷，在美国每年约有 40,000 例新生儿患有该病。CHD 患儿中约有 30%至 42%存在营养不良和喂养不耐受（FI），这与住院时间延长和死亡率增加有关。CHD 手术修复所需的体外循环（CPB）会引起全身炎症反应，使肠道菌群失调恶化，并导致肠道上皮屏障功能障碍（EBD），这可能是术后 FI 的原因之一。本研究旨在确定心脏手术后小儿 CHD 患者术后 FI 与肠道微生物组、短链脂肪酸（SCFA）和 EBD 的关系。这是一项前瞻性研究，纳入了年龄在 0-15 岁、接受 CPB 心脏手术的患者。在术前和术后采集样本，以评估肠道微生物组、血浆 EBD 标志物、短链脂肪酸（SCFA）和血浆细胞因子。收集临床数据计算 FI 评分，并评估术后患者状态。共纳入 26 例 CPB 患者，其中 13 例发生 FI。发生 FI 的患者微生物群发生了独特的变化，产 SCFA 的 、 和 减少。发生 FI 的患者，其血浆 EBD 标志物 Claudin-2（<0.05）、Claudin-3（<0.01）和脂肪酸结合蛋白（<0.01）水平升高。FI 患者的血浆和粪便 SCFA 降低。中介分析显示，FI 患者粪便丁酸和丙酸减少与微生物群功能转移有关。总之，我们提供了新的证据，表明肠道菌群失调、EBD 标志物和 SCFA 耗竭与 FI 有关。这些数据将有助于确定机制和治疗方法，以改善小儿心脏手术后的临床结局。喂养不耐受是小儿心脏手术后发病率的一个重要因素。肠道微生物群和微环境在肠道功能中起着至关重要的作用。短链脂肪酸是共生菌产生的肠道和心脏保护性代谢物，有助于维持适当的屏障功能。这些代谢物的耗竭和屏障功能障碍导致心脏手术后的喂养不耐受。确定改善肠道微环境的机制靶点，以改善营养和临床结局，这是至关重要的。
