The microbiota-immune axis as a central mediator of gut-brain communication.

Intestinal inflammatory disorders are associated with neurophysiological and behavioral symptoms. Conversely, many disorders of the central nervous system (CNS) are accompanied by intestinal complications. These observations suggest that intestinal and nervous system physiologies are functionally linked. Indeed, a growing body of literature has revealed multiple pathways mediating bidirectional communication between the intestine and the CNS, collectively referred to as the gut-brain axis. In particular, microbes naturally colonizing the mammalian gastrointestinal (GI) tract, termed the gut microbiota, not only correlate with but also play a causative role in regulating CNS function, development and host behavior. Despite these findings, our understanding of the cellular and molecular mechanisms that mediate gut-brain communication remains in its infancy. However, members of the gut microbiota have been established as potent modulators of intestinal, systemic and CNS-resident immune cell function, suggesting that gut-brain interactions may involve the host immune system. Multiple CNS disorders with gut microbiota associations, including neuroinflammatory, neuropsychiatric and neurodegenerative disorders, also have significant inflammatory manifestations. In this review, I discuss recent advances exploring the role of microbiota-immune interactions as a critical regulator of the gut-brain axis in the context of CNS and related disorders.