Mechanisms of Neural Response to Gastrointestinal Nutritive Stimuli: The Gut-Brain Axis

Background & Aims The gut-brain axis, which transmits nutrient information from the gastrointestinal tract to the brain, is important for the detection of dietary nutrients. We used functional magnetic resonance imaging of the rat forebrain to investigate how this pathway conveys nutrient information from the gastrointestinal tract to the brain. Methods We investigated the contribution of the vagus nerve by comparing changes of blood oxygenation level–dependent signals between 24 control rats and 22 rats that had undergone subdiaphragmatic vagotomy. Functional data were collected under α-chloralose anesthesia continuously 30 minutes before and 60 minutes after the start of intragastric infusion of l -glutamate or glucose. Plasma insulin, l -glutamate, and blood glucose levels were measured and compared with blood oxygenation level–dependent signals. Results Intragastric administration of l -glutamate or glucose induced activation in distinct forebrain regions, including the cortex, hypothalamus, and limbic areas, at different time points. Vagotomy strongly suppressed l -glutamate–induced activation in most parts of the forebrain. In contrast, vagotomy did not significantly affect brain activation induced by glucose. Instead, blood oxygenation level–dependent signals in the nucleus accumbens and amygdala, in response to gastrointestinal glucose, varied along with fluctuations of plasma insulin levels. Conclusions These results indicate that the vagus nerve and insulin are important for signaling the presence of gastrointestinal nutrients to the rat forebrain. These signal pathways depend on the ingested nutrients.