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Updated: Aug 21, 2026
Investigating Intestinal Barrier Breakdown in Living Organoids
Published on: March 26, 2020
Breaking the Barrier: Pro-inflammatory Stool from Infants with CHD Triggers Barrier Dysfunction within Intestinal
Monalisha Elango1, Kirtana Arikath Bs2, Haowen Qiu3
1Department of Pediatrics, Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68102, USA.
Insights
Post-operative gut bacteria from infants with congenital heart disease (CHD) cause intestinal injury after heart surgery. Organoid models reveal how these changes impact gut barrier function and healing.
Area of Science:
- Gastroenterology
- Pediatric Cardiology
- Microbiology
Background:
- Infants with congenital heart disease (CHD) undergoing cardiopulmonary bypass (CPB) often experience gut injury and barrier dysfunction.
- The impact of the post-operative gut environment on intestinal epithelium is not well understood.
- Ethical limitations in obtaining patient tissue make organoids a valuable alternative for studying post-CPB intestinal changes.
Purpose of the Study:
- To investigate the effects of post-operative gut milieu on intestinal epithelium in a model of congenital heart disease (CHD) and cardiopulmonary bypass (CPB).
- To utilize porcine intestinal organoids to model luminal exposure and assess epithelial responses to pre- and post-operative fecal supernatants.
Main Methods:
- Porcine intestinal organoids were modified for apical-out polarity to allow direct luminal exposure.
- Organoids were treated with fecal supernatants from a neonate with CHD undergoing CPB and a non-CHD control.
- Microbial composition, metabolite profiles, and epithelial responses (including tight junction proteins and signaling pathways) were analyzed after 72-hour exposure.
Main Results:
- Post-CPB stool showed reduced microbial diversity, increased pro-inflammatory organisms, elevated eicosanoids, and depleted short-chain fatty acids (SCFAs).
- Exposure to post-CPB fecal supernatant induced epithelial barrier dysfunction and injury, altering Claudin-2/3 expression and reducing fatty acid binding protein 2.
- Significant alterations in prostaglandin E2 (PGE2) signaling were observed, including changes in synthase, dehydrogenase, and EP2 receptor localization.
Conclusions:
- Post-operative stool following CPB contributes to epithelial injury and maladaptive responses in the gut.
- These responses involve remodeling of the PGE2 signaling axis, tight junction reorganization, and loss of mature enterocyte characteristics.
- This organoid model provides a powerful platform for studying gut injury after CPB and identifying therapeutic targets.
Background:
Infants with congenital heart disease (CHD) undergoing cardiopulmonary bypass (CPB) frequently develop gut injury and barrier dysfunction. The effects of the post-operative gut milieu on the intestinal epithelium remain poorly defined. Given ethical challenges in obtaining intestinal tissue from these patients, organoids offer a solution to study post-CPB intestinal changes.
Methods:
Porcine intestinal organoids were converted from basal-out to apical-out polarity to enable luminal exposure. Organoids were treated with pre-operative and post-operative fecal supernatants derived from a neonate with CHD undergoing CPB and a non-CHD surgical control. Microbial composition and metabolite profiles were analyzed, and epithelial responses were assessed following 72-hour exposure.
Results:
Apical-out organoids enabled direct luminal interrogation. Post-CPB stool exhibited enriched pro-inflammatory organisms and reduced microbial diversity, increased pro-inflammatory eicosanoids, and depletion of SCFA versus control. Post-CPB fecal supernatant induced epithelial barrier dysfunction and injury with redistribution of Claudin-2 and Claudin-3, and reduced fatty acid binding protein 2. There was altered PGE2 signaling including upregulation of PGE2 synthase, downregulation of prostaglandin dehydrogenase, and altered EP2 receptor localization.
Conclusion:
Post-operative stool following CPB contributes to epithelial injury and maladaptive responses characterized by PGE2-axis remodeling, tight junction reorganization, and loss of mature enterocyte features. This model of CHD stool exposure in organoids provides a robust translational platform for mechanistic studies and therapeutic targeting of gut injury following CPB.
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