There is now strong evidence from animal studies that gut microorganism can activate the vagus nerve and that such activation plays a critical role in mediating effects on the brain and behaviour. The vagus appears to differentiate between non-pathogenic and potentially pathogenic bacteria even in the absence of overt inflammation and vagal pathways mediate signals that can induce both anxiogenic and anxiolytic effects, depending on the nature of the stimulus. Certain vagal signals from the gut can instigate an anti-inflammatory reflex with afferent signals to the brain activating an efferent response, releasing mediators including acetylcholine that, through an interaction with immune cells, attenuates inflammation. This immunomodulatory role of the vagus nerve may also have consequences for modulation of brain function and mood.What is currently lacking are relevant data on the electrophysiology of the system. Certainly, important advances in our understanding of the gut-brain and microbiome- gut-brain axis will come from studies of how distinct microbial and nutritional stimuli activate the vagus and the nature of the signals transmitted to the brain that lead to differential changes in the neurochemistry of the brain and behaviour.Understanding the induction and transmission of signals in the vagus nerve may have important implications for the development of microbial-or nutrition based therapeutic strategies for mood disorders.