Rhythm of digestion: keeping time in the gastrointestinal tract

1. The best characterized mammalian circadian rhythms follow a light-entrained central master pacemaker in the suprachiasmatic nucleus and are associated with fluctuations in the activities of clock genes, including Clock, Bmal1, Per and Cry, the products of which bind to sequences in the promoters of effector genes. This is the central clock. 2. In the present review, we discuss evidence for an independent, but interacting, gut-associated circadian clock, the peripheral clock, which is entrained by food. 3. Disruption of circadian rhythms is associated with a wide range of pathologies, most prominently metabolism linked, but the effects of disruption of circadian rhythms on the digestive system are less well studied, although also likely to lead to functional consequences. There are clues suggestive of links between gastrointestinal disorders related to inflammation, cancer and motility and disruption of peripheral rhythms. Research aimed at understanding these links is still in its infancy. 4. We also discuss practical aspects of the presence of circadian rhythms in gastrointestinal tissues for researchers related to experimental design, data interpretation and the choice of animal models. 5. There is currently sufficient evidence to suggest that circadian rhythms are important to gut function, metabolism and mucosal defence and that further investigation will uncover connections between disordered rhythms and gastrointestinal malfunction.