Meal-Sensing Signaling Pathways in Functional Dyspepsia

Abstract

The upper gastrointestinal tract plays an important role in sensing the arrival, amount and chemical composition of a meal. Ingestion of a meal triggers a number of sensory signals in the gastrointestinal tract. These include the response to mechanical stimulation (e.g., gastric distension), from the presence of food in the gut, and the interaction of various dietary nutrients with specific "taste" receptors on specialized enteroendocrine cells in the small intestine culminating in the release of gut hormones. These signals are then transmitted to the brain where they contribute to food intake regulation by modulating appetite as well as feedback control of gastrointestinal functions (e.g., gut motility). There is evidence that the sensitivity to these food related stimuli is abnormally enhanced in functional dyspepsia leading to symptoms such nausea and bloating. In addition, these gut-brain signals can modulate the signaling pathways involved in visceral pain. This review will discuss the role of gut-brain signals in appetite regulation and the role dysregulation of this system play in functional dyspepsia.

Keywords: chemosensation; functional dyspepsia; gastrointestinal tract; mechanosensation; pain; vagal afferents.

Figure 1

Schematic of how gastrointestinal vagal afferents can be involved in the symptoms associated with functional dyspepsia. For simplicity not all neural pathways and regions are illustrated. The NTS receives input from vagal afferents innervating the gastrointestinal tract. Distinct neural outputs from the NTS coordinate sensations such as satiety, bloating and nausea. Further, neural output from the NTS to the central amygdala can modulate the processing of nociceptive information, from the spinal cord and brainstem, within the central amygdala. NTS, nucleus tractus solitarius; DMV, dorsal motor nucleus of the vagus; PBN, Parabrachial nucleus.