Zitong Zhao, Siyan Wu, Tingting Wang, Yue Zhao
Emerging studies have revealed that disruptions in circadian crosstalk between the gut microbiota and the host play an essential role in the pathogenesis of metabolic disorders. Under physiological conditions, host circadian clocks regulate microbial diurnal oscillations through rhythmic behaviors, including feeding patterns and sleep-wake cycles. This temporal regulation manifests as robust 24-hour oscillations in microbial community composition, spatial organization, and metabolic activity. These rhythmic microbial signals and their metabolic outputs are subsequently translated into host immune modulation, establishing a bidirectional temporal dialogue between the host and microbiota. Modern lifestyle disruptions, including erratic eating patterns and shift work, desynchronize this temporal dialogue, leading to the loss of microbial rhythms, impaired intestinal barrier function, maladaptive immune responses, chronic inflammation, and systemic metabolic dysregulation. This review delineates the mechanisms through which host-microbiota circadian crosstalk governs immunometabolic homeostasis, provides a mechanistic framework for understanding immunometabolic diseases, and highlights therapeutic strategies that target microbial rhythms to reset host immunity and metabolism.