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
{"title":"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。","authors":"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","doi":"10.1152/ajpgi.00151.2024","DOIUrl":null,"url":null,"abstract":"<p><p>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 (<i>n</i> = 13). Patients with FI had unique microbial shifts with the reduced SCFA-producing organisms <i>Rothia</i>, <i>Clostridium innocuum</i>, and <i>Intestinimonas</i>. Patients who developed FI had associated elevations in the plasma EBD markers claudin-2 (<i>P</i> < 0.05), claudin-3 (<i>P</i> < 0.01), and fatty acid binding protein (<i>P</i> < 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.<b>NEW & NOTEWORTHY</b> 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.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Feeding intolerance after pediatric cardiac surgery is associated with dysbiosis, barrier dysfunction, and reduced short-chain fatty acids.\",\"authors\":\"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\",\"doi\":\"10.1152/ajpgi.00151.2024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (<i>n</i> = 13). Patients with FI had unique microbial shifts with the reduced SCFA-producing organisms <i>Rothia</i>, <i>Clostridium innocuum</i>, and <i>Intestinimonas</i>. Patients who developed FI had associated elevations in the plasma EBD markers claudin-2 (<i>P</i> < 0.05), claudin-3 (<i>P</i> < 0.01), and fatty acid binding protein (<i>P</i> < 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.<b>NEW & NOTEWORTHY</b> 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.</p>\",\"PeriodicalId\":7725,\"journal\":{\"name\":\"American journal of physiology. Gastrointestinal and liver physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of physiology. Gastrointestinal and liver physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1152/ajpgi.00151.2024\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Gastrointestinal and liver physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/ajpgi.00151.2024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Feeding intolerance after pediatric cardiac surgery is associated with dysbiosis, barrier dysfunction, and reduced short-chain fatty acids.
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.
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.