Gastrointestinal hormones and the dialogue between gut and brain

Abstract

The landmark discovery by Bayliss and Starling in 1902 of the first hormone, secretin, emerged from earlier observations that a response (pancreatic secretion) following a stimulus (intestinal acidification) occurred after section of the relevant afferent nerve pathway. Nearly 80 years elapsed before it became clear that visceral afferent neurons could themselves also be targets for gut and other hormones. The action of gut hormones on vagal afferent neurons is now recognised to be an early step in controlling nutrient delivery to the intestine by regulating food intake and gastric emptying. Interest in these mechanisms has grown rapidly in view of the alarming global increase in obesity. Several of the gut hormones (cholecystokinin (CCK); peptide YY 3-36 (PYY 3-36 ); glucagon-like peptide-1 (GLP-1)) excite vagal afferent neurons to activate an ascending pathway leading to inhibition of food intake. Conversely others, e.g. ghrelin, that are released in the inter-digestive period, inhibit vagal afferent neurons leading to increased food intake. Nutrient status determines the neurochemical phenotype of vagal afferent neurons by regulating a switch between states that promote orexigenic or anorexigenic signalling through mechanisms mediated, at least partly, by CCK. Gut-brain signalling is also influenced by leptin, by gut inflammation and by shifts in the gut microbiota including those that occur in obesity. Moreover, there is emerging evidence that diet-induced obesity locks the phenotype of vagal afferent neurons in a state similar to that normally occurring during fasting. Vagal afferent neurons are therefore early integrators of peripheral signals underling homeostatic mechanisms controlling nutrient intake. They may also provide new targets in developing treatments for obesity and feeding disorders.

Physical activity level is impaired and diet dependent in preterm newborn pigs

“…In our preliminary studies on the volume of intestinal serotonergic cells in experiment 2, we found an increase from middle to distal gradient in the volume density, and enteral nutrition with BC tended to increase the volume density of serotonergic cells distally, relative to IF and TPN. Correspondingly, the distal part of the intestine is also more sensitive to the trophic effects of enteral diet than the proximal region (see Table 2 for experiments 1 and 2), probably because of a larger number of enteroendocrine and immune cells mediating these effects (9). Our analyses of the diet-dependent secretion of serotonin also suggested that MEN-BC pigs had higher serotonin levels in platelet-free plasma, relative to TPN pigs, with intermediate values for MEN-IF pigs.…”

“…There is rapidly increasing evidence of functional links among the gastrointestinal tract (GIT), the diet, and the brain, especially in early life (9). Growth rate and nutrient intakes in early life may affect later neuromuscular and cognitive outcomes, but the mechanisms are largely unknown (10).…”

Fasting does not induce gastric emptying in rats

“…Hence, this constant stimulation is a major stimulus to gastric emptying [17][18][19][20] along with many hormones, such as cholecystokinin; and neural pathways, such as parasympathetic stimuli.…”

<b>The menstrual cycle influences the gastric emptying of </b><b>alcohol </b>

“…We could not measure the plasma CCK concentrations in the present study, because we did not get the permission from the Ethical Committer to draw the blood from the participant. However, the role of CCK in the inhibition of gastric emptying was suggested to be mediated via CCK-1Rs on the vagal afferent nerve terminals distributed on the stomach and upper small intestine (7,23). That is, CCK released from endocrine cells (I cells) in the upper small intestine could bind CCK-1Rs directly (via a paracrine pathway) without any increase in the plasma CCK level.…”