Development of a Gut Model for Analyzing Impact of Surgical Intervention in Short Bowel Syndrome

Studying surgical intervention on nutrient absorption in short bowel syndrome (SBS) is challenging due to disease rarity. Animal models are expensive, time consuming, and fail to accurately mimic human SBS physiology. We hypothesized that a parameterized gut model could accurately quantify glucose absorption as intestinal length and diameter are altered using a neonatal, 2-year-old, and adolescent subject.

To analyze total bolus movement and nutrient uptake, we created an analytic expression using the Darcy-Weisbach equation. Glucose absorption was calculated for an average adolescent, 2-year-old, and neonate. Bowel length was decreased to model SBS and bowel diameter adjusted up to 2-times the normal size to simulate maladaptive dilation. Absorption, abs, is predicted in terms of diameter, D_b, and length, L_b, as abs∝L_b^3/2/D_b^5/2.

Bowel diameter, length, and SBS length were determined as follows: adolescent: 23 mm diameter, 575 cm length, 200 cm SBS; 2-year-old: 15 mm diameter, 350 cm length, 175 cm SBS; neonate: 12 mm diameter, 250 cm length, 125 cm SBS. Absorption was estimated at 80 mmol/h/25 cm with a 140 mM glucose bolus. At full length, adolescent and child absorption remained 100% until 1.5x normal bowel diameter. Neonate absorption declined at 1.1x diameter. In SBS with no dilation, absorption was 54% (adolescent), 98% (child), and 45% (neonate). All three SBS models declined along a negative exponential curve with dilation without a plateau of stable absorption.

Our model suggests that neonates with SBS are highly susceptible to malabsorption with even a low degree of dilation. Earlier autologous reconstruction may be beneficial. We hope this platform will facilitate future testing of surgical interventions to optimize procedure and timing.