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Peer-reviewedCC BY-NC-ND 4.0Scientific Reports

Pediatric intestinal enteroids derived from very early onset inflammatory bowel disease reveal differences in growth, morphology, and barrier function

5 affiliations
  1. 1The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu 632 004 India
  2. 2Centre for Stem Cell Research (CSCR), a unit of BRIC-Institute for Stem Cell Science and Regenerative Medicine (BRIC-inStem, Bengaluru), Christian Medical College, Bagayam Campus, Vellore, India
  3. 3Department of Gastroenterology, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
  4. 4Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX USA
  5. 5Tufts Medical Center, Tufts University School of Medicine, Boston, MA USA

Abstract

Pediatric inflammatory bowel disease (IBD) presents more aggressively than adult-onset disease; however, epithelial pathophysiology remains poorly understood due to limited access to patient tissue. Human intestinal enteroids (HIEs) are a powerful model for investigating disease phenotypes and heterogeneity. We characterised duodenal HIEs from two cases with Crohn’s disease (ED-71 and ED-81) and one control with intestinal obstruction (ED-19), all aged <2years. Analyses included growth curves, epithelial cell heights, immunofluorescence, histology, electron microscopy, gene expression and intestinal permeability. All HIEs maintained consistent growth in vitro, with ED-81 displaying the steepest trajectory. Morphological examination revealed variations in epithelial cell height, with ED-71 and ED-81[median(95%CI): 10.2(7.76–11.4) and 12.5(11.5–15)µm] displaying a more flattened appearance than ED-19[18.7(16.8–21.0)µm, p-value:<0.001]. HIE differentiation into intestinal cell types was confirmed by gene expression and microscopy. Intestinal permeability assays indicated compromised barrier integrity in IBD-derived monolayers, with ED-81 exhibiting the highest baseline permeability (5.27%) and EGTA-induced disruption (50.03%) compared to ED-19 (3.88% and 36.82%). Pediatric intestinal enteroids in IBD demonstrate differences in epithelial growth, morphology, and barrier function. HIEs serve as a potential translational model for pediatric IBD, facilitating the study of epithelial pathophysiology and guiding precision therapy. Further studies with more pediatric HIEs are needed to confirm these findings.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-62289-6.

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BibTeX
@article{vijayalekshmi2026pediatric,
  title = {{Pediatric intestinal enteroids derived from very early onset inflammatory bowel disease reveal differences in growth, morphology, and barrier function}},
  author = {B. Vijayalekshmi and Bhuvaneswari Selvam and B. Sandya Rani and Amit K. Dutta and A. J. Joseph and Ebby Simon and Sasirekha Ramani and Mary K. Estes and Honorine Ward and Anna Pulimood and Sitara S. R. Ajjampur},
  journal = {Scientific Reports},
  year = {2026},
  month = aug,
  doi = {10.1038/s41598-026-62289-6},
  url = {https://doi.org/10.1038/s41598-026-62289-6},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Pediatric intestinal enteroids derived from very early onset inflammatory bowel disease reveal differences in growth, morphology, and barrier function
AU  - B. Vijayalekshmi
AU  - Bhuvaneswari Selvam
AU  - B. Sandya Rani
AU  - Amit K. Dutta
AU  - A. J. Joseph
AU  - Ebby Simon
AU  - Sasirekha Ramani
AU  - Mary K. Estes
AU  - Honorine Ward
AU  - Anna Pulimood
AU  - Sitara S. R. Ajjampur
PY  - 2026
DA  - 2026/08/05
JO  - Scientific Reports
DO  - 10.1038/s41598-026-62289-6
UR  - https://doi.org/10.1038/s41598-026-62289-6
AB  - Pediatric inflammatory bowel disease (IBD) presents more aggressively than adult-onset disease; however, epithelial pathophysiology remains poorly understood due to limited access to patient tissue. Human intestinal enteroids (HIEs) are a powerful model for investigating disease phenotypes and heterogeneity. We characterised duodenal HIEs from two cases with Crohn’s disease (ED-71 and ED-81) and one control with intestinal obstruction (ED-19), all aged <2years. Analyses included growth curves, epithelial cell heights, immunofluorescence, histology, electron microscopy, gene expression and intestinal permeability. All HIEs maintained consistent growth in vitro, with ED-81 displaying the steepest trajectory. Morphological examination revealed variations in epithelial cell height, with ED-71 and ED-81[median(95%CI): 10.2(7.76–11.4) and 12.5(11.5–15)µm] displaying a more flattened appearance than ED-19[18.7(16.8–21.0)µm, p-value:<0.001]. HIE differentiation into intestinal cell types was confirmed by gene expression and microscopy. Intestinal permeability assays indicated compromised barrier integrity in IBD-derived monolayers, with ED-81 exhibiting the highest baseline permeability (5.27%) and EGTA-induced disruption (50.03%) compared to ED-19 (3.88% and 36.82%). Pediatric intestinal enteroids in IBD demonstrate differences in epithelial growth, morphology, and barrier function. HIEs serve as a potential translational model for pediatric IBD, facilitating the study of epithelial pathophysiology and guiding precision therapy. Further studies with more pediatric HIEs are needed to confirm these findings.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-62289-6.
SN  - 2045-2322
ER  -