The Vagus Nerve Regulates Immunometabolic Homeostasis in the Ovine Fetus near Term: The Impact on Terminal Ileum

Abstract

'Marc Courchesne' 'Karen Nygard' 'Patrick Burns' 'André Desrochers' 'Gilles Fecteau' 'Christophe Faure' 'Martin G. Frasch' 'Yansheng Du'] Simple Summary The brain senses and regulates all internal bodily processes, including the levels of the sugar molecule glucose in the blood stream (systemic regulation) or in specific organs, such as the gut. The contribution of the vagus nerve to this mechanism, the longest nerve connecting the brain with the rest of the body, has not been well understood. Moreover, it has remained unknown how the activity of the vagus nerve contributes to the inflammatory response as may be seen during infections when the immune system is activated. Here, we mechanically and electrically manipulated the vagus nerve activity, decreasing or increasing it selectively, and measuring the degree of change in the glucose levels and of the inflammatory response systemically and in the gut, an important site of neonatal injury. We reported a surprising dual (hormetic) anti- or pro-inflammatory effect of reduced vagal activity combined with increased levels of glucose dependent on the levels of the infectious agent inducing the inflammatory response. We further discussed the implications for future research and clinical practice. Abstract BACKGROUND. Glucosensing elements are widely distributed throughout the body and relay information about circulating glucose levels to the brain via the vagus nerve. However, while anatomical wiring has been established, little is known about the physiological role of the vagus nerve in glucosensing. The contribution of the vagus nerve to inflammation in the fetus is poorly understood. Increased glucose levels and inflammation act synergistically when causing organ injury, but their interplay remains incompletely understood. We hypothesized that vagotomy (Vx) will trigger a rise in systemic glucose levels and this will be enhanced during systemic and organ-specific inflammation. Efferent vagus nerve stimulation (VNS) should reverse this phenotype. METHODS.