Several studies have shown that the gut microbiota influences behavior and, in turn, changes in the immune system associated with symptoms of depression or anxiety disorder may be mirrored by corresponding changes in the gut microbiota. Although the composition/function of the intestinal microbiota appears to affect the central nervous system (CNS) activities through multiple mechanisms, accurate epidemiological evidence that clearly explains the connection between the CNS pathology and the intestinal dysbiosis is not yet available. The enteric nervous system (ENS) is a separate branch of the autonomic nervous system (ANS) and the largest part of the peripheral nervous system (PNS). It is composed of a vast and complex network of neurons which communicate via several neuromodulators and neurotransmitters, like those found in the CNS. Interestingly, despite its tight connections to both the PNS and ANS, the ENS is also capable of some independent activities. This concept, together with the suggested role played by intestinal microorganisms and the metabolome in the onset and progression of CNS neurological (neurodegenerative, autoimmune) and psychopathological (depression, anxiety disorders, autism) diseases, explains the large number of investigations exploring the functional role and the physiopathological implications of the gut microbiota/brain axis.