Host-microbe interactions are facilitated by the framework of the gut-brain axis. This bidirectional communication system describes a complex network of signaling pathways with neural and humoral channels. Both microbial cellular components and metabolites can interact with key pillars of the gut-brain axis via neuroimmune and neuroendocrine routes, and via the elements of the autonomic nervous system. In addition, the direct and indirect impact of the gut microbiota on host metabolic pathways can regulate the supply of neuroactive molecules and their precursors to the CNS. Important examples include the vagus nerve, the production of short chain fatty acids and the regulation of tryptophan metabolism. Research supports the involvement of the gut microbiota in a range of neural functions such as myelination, microglia activity, neuronal morphology, and blood–brain barrier integrity. These signaling pathways allow a broad scope of impact of the gut microbiota on host physiology, brain function, and behavior across the life span.