The brain-gut-microbiome axis (BGM) has emerged as a critical interface between the gut microbiome and the central nervous system (CNS), integrating the gastrointestinal, immune, and central nervous systems. Preclinical and clinical studies have demonstrated bidirectional interactions within this axis, with gut microbes communicating through nervous, endocrine, and immune signaling mechanisms. The brain can influence gut microbiota structure and function via the autonomic nervous system, modulating gut motility, transit, and permeability. Conversely, the gut microbiome can affect brain function and behavior through metabolites such as short-chain fatty acids (SCFAs) and tryptophan metabolites, which interact with enteroendocrine cells (EECs) and enterochromaffin cells (ECCs). These interactions are mediated by the vagus nerve and other pathways, influencing emotional behaviors, anxiety, depression, and cognitive functions. The BGM axis is implicated in various disorders, including irritable bowel syndrome (IBS), obesity, psychiatric conditions like depression and anxiety, and neurologic disorders such as Parkinson's disease and autism spectrum disorders. Preclinical studies have shown that altering the gut microbiome can modulate these disorders, while clinical studies are beginning to explore the potential of probiotics and other interventions. However, translating preclinical findings to human therapies remains challenging due to host-specific interactions and the complex nature of the BGM axis. Future research should focus on large-scale, controlled human studies to better understand the causes and sequelae of dysbiosis and to develop personalized treatments.The brain-gut-microbiome axis (BGM) has emerged as a critical interface between the gut microbiome and the central nervous system (CNS), integrating the gastrointestinal, immune, and central nervous systems. Preclinical and clinical studies have demonstrated bidirectional interactions within this axis, with gut microbes communicating through nervous, endocrine, and immune signaling mechanisms. The brain can influence gut microbiota structure and function via the autonomic nervous system, modulating gut motility, transit, and permeability. Conversely, the gut microbiome can affect brain function and behavior through metabolites such as short-chain fatty acids (SCFAs) and tryptophan metabolites, which interact with enteroendocrine cells (EECs) and enterochromaffin cells (ECCs). These interactions are mediated by the vagus nerve and other pathways, influencing emotional behaviors, anxiety, depression, and cognitive functions. The BGM axis is implicated in various disorders, including irritable bowel syndrome (IBS), obesity, psychiatric conditions like depression and anxiety, and neurologic disorders such as Parkinson's disease and autism spectrum disorders. Preclinical studies have shown that altering the gut microbiome can modulate these disorders, while clinical studies are beginning to explore the potential of probiotics and other interventions. However, translating preclinical findings to human therapies remains challenging due to host-specific interactions and the complex nature of the BGM axis. Future research should focus on large-scale, controlled human studies to better understand the causes and sequelae of dysbiosis and to develop personalized treatments.