There is another recent discovery to highlight how little we know about our nervous system. Theories are accepted because we believe we have a handle on the anatomy, physiology, biochemistry and biophysics of the nervous systems. But the ‘facts’ change regularly. This time it is connections between the gut and the brain – a direct sensory path and a door through which viruses can pass from gut to brain.

The paper (see citation below) deals with a type of cell in the gut lining that has been thought to communicate with the brain via hormone secretion. The researchers have shown that the cells are in physical contact with neurons and communicate directly. Further, they show that viruses can pass through that physical contact and enter a neuron. This research adds another layer of communication between gut and brain.

The cells, called enteroendocrine cells, are sensory cells reacting to chemicals in the gut. It was thought that the cells produced hormones that traveled through the bloodstream to sensory neurons. This may still be true but it is now known that the enteroendocrine cells grow long processes, neuropods, that reach nerves and form synaptic-like contact with the nerves. They are accompanied by enteric glia cells and respond to neurotrophins.

This communication is important. “Satiety, food preference, and even mood behaviors are a few of the functions modulated by gut chemosensation. Ingested nutrients and bacterial by-products contacting the gut epithelium stimulate enteroendocrine cells.”

Here is the abstract: “Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit’s functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems.”



Bohórquez, D., Shahid, R., Erdmann, A., Kreger, A., Wang, Y., Calakos, N., Wang, F., & Liddle, R. (2015). Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells Journal of Clinical Investigation DOI: 10.1172/JCI78361