Gut Microbiota-Mediated Modulation of Circadian Rhythms: Physiological and Molecular Impacts of Dietary Composition and Feeding Time

Circadian rhythms regulate fundamental aspects of physiology and behavior. The disruption of circadian rhythms has been associated with metabolic disorders, cardiovascular disease, obesity, and impaired immune function. Feeding behavior and gut microbiota represent two essential nodes within this regulatory network, as both are highly responsive to environmental cues such as diet composition and sleep-wake cycles. Research has shown that high-fat diets, excessive fructose, and chronic alcohol consumption perturb peripheral circadian rhythms and impair metabolic pathways, contributing to obesity and insulin resistance. Conversely, dietary interventions such as time-restricted feeding and macronutrient-specific entrainment can restore rhythmic gene expression and prevent metabolic pathologies. The gut microbiota plays a central role in mediating these effects through its diurnal oscillations in community composition and metabolite production, particularly short-chain fatty acids, which act as systemic cues for host circadian clocks. Disruption of microbial rhythmicity, whether through irregular eating schedules, jet lag, or environmental pollutants, can exacerbate circadian misalignment and metabolic dysfunction. Recent findings highlight a bidirectional relationship between the host circadian system and the microbiota, underscoring their interdependence in maintaining metabolic homeostasis and gastrointestinal integrity. Although preclinical models have produced mechanistic insights, the translation to humans remains limited by methodological variability and incomplete characterization of signaling pathways. This review synthesizes the current knowledge on diet-microbiota-circadian interactions and discusses potential therapeutic strategies, including dietary modulation and natural products, to mitigate circadian misalignment and its associated health risks.