A new gastric-emptying mouse model based on in vivo non-invasive bioluminescence imaging

Abstract

Different techniques were used to assess gastric emptying (GE) in small animals; most of them require sophisticated equipment, animal sacrifice and are expensive. In the present investigation a simple, non-invasive method based on bioluminescence imaging (BLI) is reported to study GE, using light-emitting Escherichia coli cells as a marker of the gastric content. A new thermostable red-emitting luciferase was chosen as reporter gene to transform E. coli cells. Bioluminescent (BL) bacteria were administered to fasting mice, after a solid meal, and in response to different doses of metoclopramide (MET) and hyoscine butylbromide (HY). Bioluminescence imaging allowed to evaluate the real time 2D spatial and temporal distribution of bacteria along the gastrointestinal tract in animals and to calculate GE rate in basal conditions and following pharmacological stimulation. The administered BL bacteria were easily imaged and localized in the stomach and subsequently followed in the duodenum and upper intestine allowing to accurately calculate GE. Gastric emptying after the test meal was significantly slower (T(1/2) 16 ± 3 min) than that obtained in fasting conditions (T(1/2) 2 ± 1 min); administration of HY (1 mg kg(-1) b.w.) significantly (P < 0.05) increased T(1/2) that was delayed up to 25 ± 4 min; MET (1 mg kg(-1) b.w.) significantly (P < 0.05) accelerated T(1/2), that was achieved within 8 ± 2 min. The reported model is simple, inexpensive, reliable, sensitive and accurate; it can detect both acceleration and slowdown of GE. The model is useful in the investigation of new drug-induced alterations of gastric motility allowing to reduce the number of experimental animals.