The gut-brain axis plays a crucial role in regulating stress-related responses, with the microbiome emerging as a key player. Diet significantly influences the microbiota-gut-brain axis, and communication between the microbiota and brain occurs through various pathways, including the vagus nerve, gut hormone signaling, the immune system, tryptophan metabolism, and microbial metabolites like short-chain fatty acids. Early life factors, such as antibiotic exposure, lack of breastfeeding, and birth mode, can alter the gut microbiota, leading to long-term effects on stress-related physiology and behavior. The gut microbiota has been implicated in conditions like anxiety, depression, and irritable bowel syndrome, although much of this evidence comes from animal studies or correlative analysis in human populations. Research on psychobiotics, which target the microbiota to improve mental health, is ongoing. The 2016 Neurobiology of Stress Workshop in Newport Beach, CA, highlighted the importance of the microbiome in development, stress, and disease, emphasizing the need for further research to understand the role of the microbiome in stress-related disorders.The gut-brain axis plays a crucial role in regulating stress-related responses, with the microbiome emerging as a key player. Diet significantly influences the microbiota-gut-brain axis, and communication between the microbiota and brain occurs through various pathways, including the vagus nerve, gut hormone signaling, the immune system, tryptophan metabolism, and microbial metabolites like short-chain fatty acids. Early life factors, such as antibiotic exposure, lack of breastfeeding, and birth mode, can alter the gut microbiota, leading to long-term effects on stress-related physiology and behavior. The gut microbiota has been implicated in conditions like anxiety, depression, and irritable bowel syndrome, although much of this evidence comes from animal studies or correlative analysis in human populations. Research on psychobiotics, which target the microbiota to improve mental health, is ongoing. The 2016 Neurobiology of Stress Workshop in Newport Beach, CA, highlighted the importance of the microbiome in development, stress, and disease, emphasizing the need for further research to understand the role of the microbiome in stress-related disorders.