Improved capacity to evaluate changes in intestinal mucosal surface area using mathematical modeling

Quantification of intestinal mucosal growth typically relies on morphometric parameters, commonly villus height, as a surrogate for presumed changes in mucosal surface area (MSA). We hypothesized that using mathematical modeling based on multiple unique measurements would improve discrimination of the effects of interventions on MSA compared to standard measures. To determine the ability of mathematical modeling to resolve differences in MSA, a mouse model with enhanced serotonin (5HT) signaling known to stimulate mucosal growth was used. 5‐HT signaling is potentiated by targeting the serotonin reuptake transporter (SERT) molecule. Selective serotonin reuptake inhibitor‐treated wild‐type (WT‐SSRI), SERT‐knockout (SERTKO), and wild‐type C57Bl/6 (WT) mice were used. Distal ileal sections were H&E‐stained. Villus height (VH), width (VW), crypt width (CW), and bowel diameter were used to calculate surface area enlargement factor (SEF) and MSA. VH alone for SERTKO and SSRI was significantly increased compared to WT, without a difference between SERTKO and WT‐SSRI. VW and CW were significantly decreased for both SERTKO and WT‐SSRI compared to WT, and VW for WT‐SSRI was also decreased compared to SERTKO. These changes increased SEF and MSA for SERTKO and WT‐SSRI compared to WT. Additionally, SEF and MSA were significantly increased for WT‐SSRI compared to SERTKO. Mathematical modeling provides a valuable tool for differentiating changes in intestinal MSA. This more comprehensive assessment of surface area does not appear to correlate linearly with standard morphometric measures and represents a more comprehensive method for discriminating between therapies aimed at increasing functional intestinal mucosa. Evaluation of changes to the intestinal mucosa commonly relies on histologic measures. Using a novel and accurate method for calculating mucosal surface area, we found significant differences between experimental groups which were missed by standard measures alone.