Immune modulation of the brain-gut-microbe axis

Only recently have we fully appreciated that the classically separated domains of neurology, endocrinology, immunology and microbiology, with their various organs- the brain, glands, gut, immune cells and microbiota, could actually be joined to each other in a multidirectional network of communication, in order to maintain homeostasis. For example, local and systemic immune activation have profound neural and behavioral effects (Campos-Rodriguez et al., 2013), neuroendocrine hormones regulate immune cytokines, and together, the nervous system and immune system work together in synergy to protect the body from infection (Steinman, 2004). Analogously, the gut microbes greatly impact the host immunological, psychological, and overall well-being of the host (Collins and Bercik, 2013; El Aidy and Kleerebezem, 2013a; Wang and Kasper, 2013; Moloney et al., 2014). However, definitive mechanisms that orchestrate a functionally relevant communication within this network, in particular, during the early life development, are yet to be elucidated. A potential unifying mechanism very likely involves multiple-functioning molecules and their receptors, as they are produced by, act upon and move from one system to another linking the brain, gut, immune system, and microbiota. These messenger molecules include (among others) neurotransmitters, neuropeptides, endocrine hormones, and cytokines.