PD315 - DISRUPTED GUT–PANCREAS SIGNALING DRIVES PANCREATIC ENDOCRINE REMODELING IN NEONATAL SHORT BOWEL SYNDROME RECEIVING PARENTERAL NUTRITION

PD315

DISRUPTED GUT–PANCREAS SIGNALING DRIVES PANCREATIC ENDOCRINE REMODELING IN NEONATAL SHORT BOWEL SYNDROME RECEIVING PARENTERAL NUTRITION

A. Nagarapu¹, S. Mehta¹, O. Al Oudat¹, A. Jain¹, A. Sims¹, K. Kurashima¹, C. Manithody¹, M. Swiderska-Syn¹, F. R. Medina Carbonell¹, A. K. Jain^1,*

¹Pediatrics, Saint Louis University School of Medicine, St. Louis, United States

Rationale: Neonatal short bowel syndrome (SBS) disrupts gut-derived signaling and leads to intestinal and hepatobiliary injury. The impact of SBS on pancreatic endocrine development is unknown. We hypothesized that neonatal SBS alters pancreatic islet cell cluster (ICC) morphology and endocrine cell composition.

Methods: Neonatal piglets (7–10 days) received enteral milk feeding (EN) or underwent 75% small bowel resection with ileocolonic anastomosis. SBS were maintained on parenteral nutrition (PN) post-operatively. A subgroup of SBS animals received prebiotic supplementation to evaluate if microbiome modulation may influence pancreatic endocrine development. Pancreatic tissue were stained for insulin, glucagon, and chromogranin A. Five 20× images per sample were analyzed using QuPath to quantify ICC size, circularity, cell number, and endocrine cell composition.

Results: SBS animals as characterized previously demonstrated features of intestinal failure including cholestasis with elevated conjugated bilirubin (3.89±0.51 vs 0.036±0.004 mg/dL in EN), increased GGT (129.97±24.11 vs 19.56±3.12 U/L), and reduced distal gut linear density (0.11±0.008 vs 0.30±0.02 g/cm). ICC frequency declined exponentially with increasing cluster size across groups. In ICCs measuring 4001–5000 µm², insulin-positive cells were lower in SBS versus EN (6.12±0.00% vs 40.59±9.02%). Within SBS, smaller ICCs (1001–2000 µm²) showed higher insulin-positive and lower glucagon-positive cell proportions compared with ICCs of 2001–3000 µm². SBS animals receiving prebiotics demonstrated greater preservation of small (1-1000 µm²) insulin-positive cell clusters.

Conclusion: SBS supported on PN is associated with hepatobiliary injury, intestinal atrophy, and altered pancreatic endocrine composition. Microbiome modulation may attenuate these changes, highlighting a potential gut–pancreas signaling axis in SBS.

Disclosure of Interest: A. Nagarapu: None declared, S. Mehta: None declared, O. Al Oudat: None declared, A. Jain: None declared, A. Sims: None declared, K. Kurashima: None declared, C. Manithody: None declared, M. Swiderska-Syn: None declared, F. Medina Carbonell: None declared, A. Jain Grant / Research Support from: NIH