Background
Currently, “rotation” of the intestine is regarded as an essential part of gut development and positional pathologies such as malrotations are explained by aberrant rotation. Recent animal and modeling studies stressed the importance of a biomechanical interaction between the gut tube and its mesentery to account for the looping pattern of the small intestine. We, therefore, have reinvestigated human gut development with an emphasis on temporal changes in position and size of the intestinal loops and their mesentery to determine the contributions of these factors to intestinal morphogenesis.

Methods
3D reconstructions of 16 human embryos from 4-10 weeks of development were created with Amira and Cinema software.

Results
The primary midgut loop formed prior herniation. Embryonic growth caused a straightening of the body axis thereby initiating a 90º “rotation” of the primary loop. Within the small-intestinal part of the primary loop four secondary loops developed in a strict spatiotemporal fashion around the central herniating mesenteric rod. These secondary loops remained traceable after herniation because of the very reproducible branching pattern of the superior mesenteric artery and the folding pattern of the mesentery. Tertiary looping appeared to follow a random pattern. During herniation, the leftward change in position was most pronounced for the proximal part of the small intestine and virtually non-existent for the distal part. In contrast, the distal intestine changed position rapidly after the herniation had resolved in such a way that the ileum and cecum ended up in the lower right abdomen.

Conclusion
This study showed a predefined pattern (“blueprint”) of primary and secondary loop development. The so-called “rotation” is due to differential growth of the embryo, followed by leftward growth of the proximal small intestine during herniation and, finally, a “passive” change in position of the distal small intestine and cecum after herniation.