Changes in gut microbiota can modulate the peripheral and central nervous systems, resulting in altered brain functioning and suggesting the existence of a microbiota gut-brain axis. Studies have identified that behavioral changes can be induced in rodents by the oral administration of specific bacterial strains and/or putative prebiotic compounds. However, The mechanisms whereby microbes in the gut may be psychoactive are not yet completely understood. They include the production of certain neurotransmitters, fermentation products such as fatty acids, and the shedding of microvesicles that recapitulate the effects of the parent bacteria. The vagus nerve has also emerged as an important means of communicating signals from gut bacteria to the brain. Further understanding of the mechanisms underlying microbiome-gut-brain communication will provide us with new insight into the symbiotic relationship between gut microbiota and their mammalian hosts and help us identify the potential for microbe-based therapeutic strategies to aid in the treatment of mood disorders. The clinical translation of this exciting and rapidly expanding field of knowledge is only just beginning to be explored in terms of stress, anxiety, depression and autism.