The mammalian intestinal epithelium is a unique model for studying cellular differentiation since it undergoes continuous and rapid renewal. Substantial new information has accumulated on the mechanisms of regulation of the gene expression (e.g. Wnt, Hedgehog, bone morphogenic proteins), and the cell proliferation and apoptosis of the intestine. New knowledge has been gained in areas of genetics, central nervous system and enteric nervous system neurotransmitters (e.g. serotonin, corticotrophin-releasing factor, endogenous cannabinoid system, pathogen associated molecular patterns) of motility, sensitivity and secretion, the effect of altered mucosal inflammation on cytokine and paracrine activation, and neural sensitization, postinfectious disorders, the influence of psychologic stress on gut functioning through alterations in regulatory pathways, and improved accuracy of diagnosis both at the gut and brain level. In addition, acknowledgement of these mechanisms might help to develop strategies for therapy of neuronal abnormalities, which cause different gastrointestinal disease (e.g. irritable bowel syndrome, Crohn's disease). The present review focuses on the relationships between the gene expression and the intestine, and furthermore, presents the evidence and gastrointestinal diseases of the autonomic nervous system, the humoral factors, and the immune functions related intestinal proliferation and apoptosis.