The molecular interplay between the gut microbiome and circadian rhythms: an integrated review
Boyang Zheng, Liwei Wang, Shilin Sun, Xingxing Yuan, Qun Liang
Abstract
This integrated review synthesizes current evidence on the molecular interplay between the gut microbiome and circadian rhythms, emphasizing a sophisticated bidirectional communication system crucial for maintaining metabolic, immune, and neurological homeostasis. The host circadian clock orchestrates microbial composition and function through rhythmic changes in feeding-fasting cycles, hormone secretion, immune responses, and bile acid metabolism. In return, microbial metabolites, including short-chain fatty acids such as butyrate, secondary bile acids like lithocholic acid, and tryptophan derivatives, act as timing cues that influence core clock gene expression via epigenetic mechanisms, receptor-mediated signaling (GPR41/43, FXR), and neuroendocrine pathways. Disruption of this finely tuned dialogue, known as chronodisruption, often driven by modern lifestyles, predisposes individuals to a range of pathologies, including metabolic syndrome, inflammatory bowel disease (IBD), neurodegenerative disorders, and cancer. The review also evaluates promising chronotherapeutic interventions such as time-restricted eating (TRE), targeted probiotic use, and chronopharmacology, which aim to resynchronize host-microbe rhythms and restore physiological balance. Elucidating these mechanisms provides a foundational framework for developing personalized health strategies that target the gut-clock axis.