Disrupted Enteric Glial Cell Circadian Oscillation: A Proposed Mechanism Linking CMM-Axis Desynchronization, Gut Jet Lag, and Chronic Functional Constipation

Chronic functional constipation is highly prevalent and frequently recurrent, and gut jet lag triggered by circadian-rhythm disruption represents an important modern-lifestyle-associated risk factor. Although the Chrono-Microbiota–Motility (CMM)-axis conceptual framework for circadian-disruption-related functional constipation has been published, existing work mainly describes macroscopic microbiota–motility crosstalk and largely overlooks enteric glial cells (EGCs) as secondary peripheral circadian relays within the gut wall. Drawing on evidence from population-based epidemiology, human colonic specimens, multi-omics studies, and animal models of circadian disruption, this review delineates the pathological mechanisms by which disrupted circadian oscillations of enteric glial cells mediate hierarchical desynchronization of the CMM axis and contribute to gut jet lag. It further outlines a progressive pathological cascade from external circadian perturbations and enteric glial cell clock disruption to host–microbiota temporal desynchronization and subsequent collapse of the colonic motility network, discusses the potential implications of this mechanism for clinical risk stratification in chronic functional constipation, and provides a theoretical basis for future basic and translational research in gut chronobiology. It should be emphasised that the integrated mechanistic framework presented herein constitutes a testable hypothesis largely built upon pre-clinical animal observations and indirect human tissue evidence, rather than an established pathophysiological reality. This framework highlights one potential interstitial branch within the complex multi-cellular gut circadian regulatory network.