The enteric nervous system (ENS) is a complex network in the gut wall, extending throughout the gastrointestinal tract and coordinating vital gastrointestinal functions, such as motility, perception, mucosal permeability and secretion, blood flow, as well as immune and inflammatory processes.¹ The ENS is connected to the central nervous system (CNS) by sympathetic and parasympathetic nerves which relay information to and from the brain via pre- and paravertebral ganglia, spinal cord, and medulla; yet, it can perfectly function independently of the CNS.

The ENS contains as many neurones as the spinal cord.¹ Enteric neurones have been neurochemically and immunohistochemically classified based on characteristic combinations of neurotransmitters, their synthesising enzymes, and neuronal markers, which ultimately constitute a “neurochemical code” (for review see Kunze and Furness²). Neurochemical coding has provided an important tool to identify functionally distinct neuronal subpopulations, and it is generally assumed that the neurochemical phenotype of differentiated postmitotic neurones is finally determined.^3,4

The most abundant cells in the ENS are glia.⁵ Enteric glia lie adjacent to neuronal cell bodies in the enteric ganglia, but probably as many of them accompany the extraganglionic nerve strands throughout all layers of the intestinal wall, from serosa to mucosa.^5–7 Enteric glia envelop neuronal cell bodies and axon bundles without producing myelin. Historically, enteric glia used to be seen as little more than packing material, holding the ENS together (“glia” derives from the Greek word for “glue”). Presently, however, evidence is accumulating to support a much more active role for glia in enteric neurotransmission and information processing (for review see Rühl⁸).

In this issue of Gut, Aubé and colleagues⁹ report exciting findings which further extend the potential roles of …