Feeding intolerance after pediatric cardiac surgery is associated with dysbiosis, barrier dysfunction, and reduced short-chain fatty acids.

IF 3.9 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Jacob Owens, Haowen Qiu, Cole Knoblich, Lisa Gerjevic, Jacques Izard, Linda Xu, Junghyae Lee, Sai Sundeep Kollala, Daryl J Murry, Jean Jack Riethoven, Jesse A Davidson, Amar B Singh, Ali Ibrahimiye, Laura Ortmann, Jeffrey D Salomon
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引用次数: 0

Abstract

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 (n = 13). Patients with FI had unique microbial shifts with the reduced SCFA-producing organisms Rothia, Clostridium innocuum, and Intestinimonas. Patients who developed FI had associated elevations in the plasma EBD markers claudin-2 (P < 0.05), claudin-3 (P < 0.01), and fatty acid binding protein (P < 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.NEW & NOTEWORTHY 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.

小儿心脏手术后的喂养不耐受与菌群失调、屏障功能障碍和短链脂肪酸减少有关。
背景:先天性心脏病(CHD)是最常见的出生缺陷,每年约有 40,000 名美国新生儿患有此病。先天性心脏病患者营养不良和喂养不耐受(FI)的比例为 30-42%,与住院时间延长和死亡率增加有关。心脏畸形手术修复所需的心肺旁路(CPB)会诱发全身炎症反应,加重肠道菌群失调并诱发肠上皮屏障功能障碍(EBD),从而可能导致术后喂养不耐受:确定小儿心脏手术后FI与肠道微生物组、短链脂肪酸(SCFA)和EBD的关系:方法:对 0-15 岁接受心脏手术并进行 CPB 的患者进行前瞻性研究。方法:对接受 CPB 心脏手术的 0-15 岁患者进行前瞻性研究,收集术前和术后样本,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。我们还收集了临床数据,以计算 FI 评分和评估患者术后状况:我们招募了 26 名 CPB 患者,发现了 FI(13 人)。FI患者的微生物发生了独特的变化,产生SCFA的微生物、轮虫、无毒梭菌和肠道菌减少。发生 FI 的患者血浆 EBD 标志物 Claudin-2(pConclusion)升高:我们提供了肠道菌群失调、EBD 标志物和 SCFA 贫乏与 FI 相关的新证据。这些数据将有助于确定机制和治疗方法,从而改善小儿心脏手术后的临床疗效。
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来源期刊
CiteScore
9.40
自引率
2.20%
发文量
104
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Gastrointestinal and Liver Physiology publishes original articles pertaining to all aspects of research involving normal or abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. Authors are encouraged to submit manuscripts dealing with growth and development, digestion, secretion, absorption, metabolism, and motility relative to these organs, as well as research reports dealing with immune and inflammatory processes and with neural, endocrine, and circulatory control mechanisms that affect these organs.
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