<p>Mediated by the bitter taste receptors (TAS2R), the perception of bitter taste does not only involve the oral cavity but various physiological systems throughout the gastrointestinal tract. The relationship between stimulation and modulation is crucial for understanding the broader implications of bitter taste signalling in health and disease. In this study, we investigated how the expression of intestinal rat Tas2r (rTas2r) is affected by natural extracts containing bitter ligands, examined their association with obesity, and their effects on GLP-1 secretion. For this, we performed subchronic stimulations with a mixture of polyphenols and individual molecules in rats. Moreover, we also examined how the individual bitter molecule (epicatechin) affects the secretory profile of intestinal enteroendocrine cells. Treating rats with procyanidins up-regulated rTas2r in all the segments of the gastrointestinal tract, with the most changes observed in the duodenum and ascending colon. Epicatechin, one of the main components of the previously used extract, had a much more specific effect, as we observed mostly changes in the jejunum, where rTas2137, -139, -143 and -144 were up-regulated. In Hutu-80 cells, epicatechin downregulated TAS2R14 after 24 hours, which limited GLP-1 secretion after acute peptone stimulation. Our results support a network effect in the role of the bitter taste receptors along the intestinal areas that must be considered to address the work with bitter agonists.</p>