There is accumulating evidence that alcohol consumption and especially alcohol withdrawal increase brain levels of known innate immune signaling molecules and cause neuroinflammation. It has been shown that microbiota play a pivotal role in this process and affect central neurochemistry and behavior. Disruption of or alterations in the intimate cross-talk between microbiome and brain may be a significant factor in many psychiatric disorders. Alterations in the composition of the microbiome, so called dysbiosis, may result in detrimental distortion of microbe-host homeostasis modulating the hypothalamic-pituitary-adrenal axis. A variety of pathologies are associated with changes in the community structure and function of the gut microbiota, suggesting a link between dysbiosis and disease etiology, including irritable bowel syndrome depression, anxiety disorders, schizophrenia, and alcoholism. Despite a paucity of clinical studies in alcohol-dependent humans, emerging data suggests that alcohol induced alterations of the microbiome may explain reward-seeking behaviors as well as anxiety, depression, and craving in withdrawal and increase the risk of developing psychiatric disorders.