Timekeepers of the gut: host circadian rhythms and microbial modulators

The intestine is more than a digestive organ. It is a system under circadian control, where cellular renewal, barrier integrity, absorption, immunity, and microbial ecology are orchestrated in time. Emerging evidence reveals that circadian rhythms not only regulate the daily turnover of intestinal epithelium but also fine-tune digestive enzyme expression, mucosal defense, and gut hormone secretion. These processes are driven by core clock proteins and synchronized by feeding cues, neural signals, and microbial metabolites. The gut microbiota consists of essential symbionts that themselves exhibit diurnal oscillations in composition and function, in turn feeding back to modulate host circadian pathways. Disruption of this host-microbiota temporal alignment, as occurs with jet lag, shift work, or high-fat diets, impairs intestinal homeostasis and elevates risk for inflammation, infection, and metabolic disorders. This review integrates evidence from mouse, zebrafish, fly, and human studies to highlight the rhythmic regulation of gut physiology, emphasizing how coordination between the host clock and microbiota sustains health. Viewing the gut as a circadian conductor underscores new opportunities for chronotherapy and microbiota-targeted interventions.