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Updated: Jun 12, 2026
Tissue Engineering of the Intestine in a Murine Model
Published on: December 1, 2012
Distal Recirculation of Enteral contents Augmented Mechanically (DREAM) Promotes Intestinal Adaptation and Restores
Shaurya Mehta1, Kento Kurashima1, Chandrashekhara Manithody1
1Department of Pediatrics, Saint Louis University School of Medicine, Saint Louis, Missouri.
Background & Aims:
Short bowel syndrome (SBS) leads to malabsorption and intestinal failure-associated liver disease. Intestinal adaptation (IA) driven by sustained enteral nutrition (EN) is essential, but EN delivery is limited after major resection. We developed DREAM (Distal Recirculation of Enteral contents Augmented Mechanically), which enables complete EN despite SBS, and enhances IA. We evaluated its efficacy in a translational large-animal model.
Methods:
The study randomized 20 neonatal pigs to EN (control), SBS (75% resection), or DREAM. Growth, serum biochemistry, cytokines, intestinal morphology, barrier integrity, hepatic histology, and gene expression (quantitative polymerase chain reaction, RNA sequencing, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology enrichment) were analyzed.
Results:
DREAM prevented hepatic and intestinal injury seen in SBS. Serum bilirubin (0.11 vs 5.14 mg/dL, P = .0008), γ-glutamyl transferase (23.2 vs 114.6 IU/L, P < .0001), and bile acids (9.7 vs 39 μmol/L, P = .0026) were significantly lower. Inflammatory cytokines (interferon-γ, P = .0296; interleukin 1β, P = .0349; and interleukin 6, P = .0189) and portal lipopolysaccharide (P = .0130) markedly improved. DREAM enhanced IA, increasing linear gut density (0.38 vs 0.209 g/cm, P < .0001), villus-to-crypt ratio (P = .0026), glucagon-like peptide 2 (P < .0001) and restored occludin and E-cadherin (P < .001). Hepatic bile salt export pump and cholesterol 7α-hydroxylase regulation were preserved (P = .0373 and P = .0034), and intestinal farnesoid X receptor, Takeda G-protein-coupled receptor 5, and epidermal growth factor signaling were reactivated (P < .01). Transcriptomic analysis confirmed improvements in metabolic, absorptive, and immune pathways. DREAM effluent demonstrated >80% macronutrient absorption within 6 hours (P < .0001).
Conclusion:
DREAM enables full EN in SBS, restoring absorption, mucosal integrity, and gut-liver homeostasis while preventing intestinal failure-associated liver disease. This approach represents a promising translational advance in SBS therapy.
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