Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the murine small intestine.

Background: Enteric serotonin influences intestinal homeostasis and functions as a mucosal growth factor. Previously, we demonstrated increased mucosal surface area and enhanced crypt cell proliferation in serotonin reuptake transporter (SERT)-deficient mice. Therefore, we hypothesized that serotonin-mediated mucosal growth would also result in enhanced carbohydrate and lipid absorption.

Material And Methods: Wild-type C57Bl/6 (WT) and SERT-knockout (SERTKO) mice were fasted then gavaged with D-xylose or boron-dipyrromethene (BODIPY) FL-C12 medium-chain fatty acid analog. Serum D-xylose and BODIPY concentrations were serially measured from blood drawn at 30 to 360 min post-gavage. Small intestine was harvested from both groups for comparison of morphometric parameters. Area under the curve of plotted graphs was calculated, and means were compared with Student's t-test to a significance of p < 0.05.

Results: Villus height and crypt depth were significantly greater in the middle and distal small intestine of SERTKO animals compared to WT. Overall absorption of D-xylose and BODIPY was greater in SERTKO animals compared to WT animals. Absorption of D-xylose was persistently elevated in SERTKO animals, while there was an initial delay in BODIPY absorption followed by a sustained and significantly greater absorption in SERTKO animals at 60-360 min after gavage.

Conclusion: Potentiation of serotonin signaling in SERTKO mice results in small intestinal mucosal growth and enhanced carbohydrate and fat absorption in vivo. These functional increases support the concept of targeting the serotonin signaling system to augment intestinal adaptation in the setting of intestinal failure.