The Triad Axis of Circadian Rhythms, Gut Microbiome, and Host Health: From Molecular Mechanisms to Integrated Therapeutic Interventions

Circadian rhythms and the gut microbiome represent two fundamental, evolutionarily conserved systems that orchestrate host physiology in synchrony with environmental cycles. Mounting evidence reveals that these systems are not merely parallel but are intricately linked in a bidirectional, self-reinforcing network, forming a critical triad axis with the host. This review synthesizes current knowledge on the molecular mechanisms underlying circadian-microbiome crosstalk, emphasizing how this axis regulates metabolic, immune, and neurological homeostasis. Disruption of circadian rhythms, through shift work, nocturnal light exposure, or erratic feeding, initiates a pathological cascade leading to microbial dysbiosis, impaired intestinal barrier function, and systemic inflammation. This triad dysfunction underpins a broad spectrum of chronic diseases, including obesity, type ۲ diabetes, non-alcoholic fatty liver disease, inflammatory bowel diseases, neuropsychiatric disorders, and cancer progression. We discuss emerging therapeutic strategies aimed at restoring rhythmic harmony, such as chrononutrition, time-restricted feeding, chronobiotics (e.g., melatonin, next-generation probiotics), chronotherapy, and personalized time-based medicine. Integrating chronobiology with microbiome science offers a transformative framework for understanding and treating modern chronic diseases, highlighting the imperative of temporal precision in health interventions.

کلیدواژه ها:

Circadian rhythms ، Gut microbiome ، Chronodisruption ، Dysbiosis ، Chrononutrition ، Chronobiotics