The Gut-Brain Axis and Circadian Regulation: From the Chronobiome to Neuroinflammation

The gut-brain axis constitutes an integrated network of neural, endocrine, immune, and metabolic communication through which the gut microbiota influences central nervous system functions, including sleep, mood, and neuroimmune responses.Recent evidence demonstrates that the microbiota exhibits diurnal rhythmicity in composition and function, modulated by feeding patterns and the host's circadian system, while microbial signals, especially metabolites, can reprogram peripheral clocks and alter metabolic and inflammatory homeostasis.Experimental studies describe how microbial oscillations contribute to the temporal organization of host metabolism and the rhythmicity of gene expression, consolidating the concept of the "chronobiome."Chronic circadian misalignment, such as from sleep deprivation, shift work, or irregular eating patterns, is associated with dysbiosis and metabolic and inflammatory changes, supporting the notion of "microbial jet lag."In the neuroimmune axis, evidence indicates that the microbiota influences microglial maturation and function and that microglia possess intrinsic circadian regulation, suggesting a temporal signature of neuroinflammation.Finally, emerging interventions such as psychobiotics and chrononutrition, including time--restricted eating strategies, are emerging as promising approaches to restore circadian synchronization and mitigate metabolic and neuroinflammatory vulnerabilities.It is concluded that the integration of microbiota, circadian rhythms, and gut-brain communication represents a central axis for preventive medicine, with the potential to guide personalized interventions based on meal timing and microbiome modulation.