Circadian regulation of gastrointestinal motility and the effect on disorders of gut-brain interaction.

Gastrointestinal (GI) motility follows a circadian rhythm regulated by a network of central and peripheral clocks, with the suprachiasmatic nucleus serving as the master clock. Disruptions to circadian rhythms are linked to impaired GI motility and disorders of gut-brain interaction, which include irritable bowel syndrome (IBS) and functional dyspepsia (FD). Emerging evidence suggests that circadian misalignment alters gut-brain interactions, exacerbating the symptoms of these disorders. Additionally, sex differences in circadian regulation contribute to variations in susceptibility. Indeed, women have a heightened sensitivity to circadian disruption, which may be attributed to the higher prevalence of IBS and FD among female patients. Recent studies highlight the role of molecular core clock components in regulating GI motor function. Moreover, interventions aimed at correcting circadian misalignment, such as exercise and time-restricted feeding, may help align peripheral clocks and show promise for mitigating GI motor dysfunction by restoring circadian rhythmicity, reducing stress responses, and improving sleep quality. These improvements may, in turn, alleviate symptoms of IBS and FD. We review the mechanisms linking circadian regulation to GI motility, the consequences of circadian disruption on the GI tract, and potential chronotherapeutic approaches to restoring circadian regulation. Understanding the interplay between circadian regulation and GI motility may lead to the development of novel, nonpharmacologic interventions to improve the GI motor function by optimizing circadian alignment.