Nutrition and defense are important functions that involve the gastrointestinal tract. In healthy subjects, meal ingestion induces homeostatic sensations (satiation and fullness) that are involved in digestive well-being and mood. However, a large proportion of the general population presents a wide range of digestive symptoms but no abnormalities that can be detected by conventional diagnostic methods.

A new narrative review, led by Dr. Christine Feinle-Bisset from the University of Adelaide (Australia), updates how the upper gastrointestinal tract responds to meal-related stimuli, both in healthy conditions and in the context of eating-related disorders.

The distension of the gastric wall is the first gastrointestinal sensing response after ingesting a meal. In a second step, macronutrients that include lipid and protein enter the small intestine lumen and what is left after digestion (i.e., fatty acids and amino acids) interact with receptors on enteroendocrine cells. This leads to a reduction in appetite and food intake involving changes in both gastrointestinal motility (e.g., pyloric motility) and gut hormones.

As such, when the body senses fatty acids and amino acids in the gastrointestinal lumen, gastrointestinal hormones (e.g., cholecystokinin and glucagon-like peptide-1) are released that act on the brain, via either activating hormone receptors on vagal afferent nerves or following transport through the bloodstream. Altogether, the subsequent transduction of mechanically- and nutrient-derived gut signals to the brain may drive changes in eating behavior. In the clinical setting, it is possible to measure the manifestations of intraluminal meal-related stimuli in a non-invasive way through the circulating levels of gut hormones, changes in upper gastrointestinal motility, and appetite perceptions and energy intake.

While the mechanisms outlined above ensure the regulation of proper gastrointestinal function, abnormalities in detecting intraluminal meal-related stimuli may occur in manifold conditions that are not necessarily related to the gut.

Here are a few examples:

  • A decreased sensitivity to gastric distension and duodenal dietary fats has been reported in people with obesity, secondary to excess energy intake. In contrast, obese people tend to maintain sensitivity to the appetite-suppressing effects of protein.
  • An enhanced sensitivity to both gastric distension and small intestinal fats accompanied by postprandial digestive symptoms has been repeatedly reported in functional gastrointestinal disorders.
  • In the critically ill, hypersensitivity to small intestinal nutrients and gastrointestinal motor dysfunctions has been shown, which hinders the provision of nutrition.
  • Anorexia nervosa and bulimia nervosa have been linked with an increased sensitivity to gastric distension and alterations in gastrointestinal hormone secretion (e.g., gastrointestinal peptides) in response to nutrients.
  • The aging process—even in healthy people—may suppress hunger perception and energy intake, which, in turn, may arise from delayed gastric meal emptying that compromises gastrointestinal sensitivity to meal-related stimuli. However, it seems that the elderly are less sensitive to the appetite-suppressant effects of nutrients and this requires further study.

On the whole, research into how gut content, sensitivity and reflex activity shape digestive sensations has shown the impact of preabsorptive signals (specifically gastric distension and small intestinal nutrients) not only on gastrointestinal functions, but also on appetite and energy intake. Although the authors highlight that understanding the mechanisms by which our gut and brain react to meal-related stimuli comes mainly from preclinical and ex-vivo studies, research in this area will help provide a better understanding of the sensory dysfunctions in eating-related disorders that are behind gastrointestinal symptoms reported by patients.

This review article belongs to the special issue “Food and Diet for Gut Function and Dysfunction” in the peer reviewed open access journal Nutrients. This issue was instigated by the European Society of Neurogastroenterology and Motility, guest edited by Profs Fernando Azpiroz and Paul Enck, and made possible through an unrestricted educational grant from Danone.



Hajishafiee M, Bitarafan V, Feinle-Bisset C. Gastrointestinal sensing of meal-related signals in humans, and dysregulations in eating-related disorders. Nutrients. 2019; 11(6). doi: 10.3390/nu11061298.