Intermittent fasting (IF) has gained increasing attention as a dietary strategy to improve metabolic health and prevent cardiometabolic disorders. Accumulating evidence suggests that modulation of the gut microbiota may represent one of the mechanisms underlying the physiological benefits of IF. This review summarizes the current knowledge on the mechanisms by which IF modulates gut microbial ecology and how these changes influence host metabolic and immune functions. We examine the effects of IF on gut microbiota diversity and composition, highlighting shifts in key microbial taxa associated with metabolic regulation. In addition, we discuss how fasting-induced microbial remodeling affects microbiota-derived metabolites, including short-chain fatty acids and bile acids, which play central roles in energy homeostasis, intestinal barrier integrity, and inflammatory signaling. Increasing evidence indicates that IF interacts with circadian rhythms, influencing both microbial oscillations and host metabolic pathways that coordinate nutrient sensing and energy metabolism. Furthermore, we explore the bidirectional crosstalk between the gut microbiota and the intestinal immune system, emphasizing that fasting-driven microbial changes may modulate inflammatory responses, epithelial barrier function, and immune cell activity. Finally, we discuss nutritional strategies that may enhance the beneficial effects of IF, including the incorporation of prebiotics, dietary fiber, and probiotic supplementation, to promote microbial diversity and functional resilience. Collectively, these findings support a model in which IF acts as a key modulator of the gut microbiota-immune-metabolic axis. Future integrative studies combining gut microbiome, metabolomic, and immunological approaches are needed to better understand these interactions and optimize microbiota-targeted dietary interventions.
