Editors' ChoiceGUT-BRAIN AXIS

Lighting the path from the gut to the brain

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Science Translational Medicine  08 Jun 2016:
Vol. 8, Issue 342, pp. 342ec92
DOI: 10.1126/scitranslmed.aag1871

Vagal nerve stimulation is used to treat epilepsy and depression and more recently has been found to be potentially beneficial for the treatment of obesity. However, the mechanism by which vagal stimulation causes weight loss is unclear. The vagus nerve innervates many intrathoracic and intra-abdominal organs to regulate their function and also contains sensory fibers that monitor intestinal nutrients and volume. Now, Williams et al. have begun to specifically examine the connections between the gut and the brain.

In initial studies, the authors monitored neural activation in vagal ganglia in vivo in mice. They found that distinct vagal subpopulations rapidly transmit information about either intestinal distension (stretch) or the presence of nutrients (food). In addition, these neural populations had discrete innervation patterns and responded to specific gut hormones. Neurons responding to stretch express glucagon-like peptide I receptor (GLP1R), innervated the intestinal muscle, and responded to the gut hormone cholecystokinin. In contrast, neurons activated by food express the G protein–coupled receptor, GPCR65, formed a plexus innervating duodenal villi, and were activated by serotonin. Next, the researchers used light to activate these neurons. Switching on the pressure-sensitive GLP1R neurons increased gastric pressure but also altered breathing and heart rate, while activating nutrient-sensing GPCR65 neurons blocked gastric contractions and reduced gastric pressure. In a final set of studies, the group examined how the information from these populations was represented in the brain. Although the GLP1R and GPCR65-expressing neurons were intermingled in the vagal ganglion, they projected to nonoverlapping regions in the brain stem.

This study shows that genetically distinct vagal neurons can monitor and control particular intestinal functions and respond to specific gastrointestinal hormones. If these pathways are present in humans, targeting their activity may allow alternative therapeutic approaches for treating obesity or abnormal intestinal motility.

E. K. Williams et al., Sensory neurons that detect stretch and nutrients in the digestive system. Cell 10.1016/j.cell.2016.05.011 (2016). [Abstract]

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