Taste is important in the selection of food and is orchestrated by a group of distinct receptors, the taste G protein-coupled receptors (GPCRs). Taste 1 receptors (Tas1rs in mice and TAS1Rs in humans; also known as T1Rs) detect sweet and umami tastes, and taste 2 receptors (Tas2rs in mice and TAS2Rs in humans; also known as T2Rs) detect bitterness. These receptors are also expressed in extraoral sites, including the gastrointestinal mucosa. Tas2rs/TAS2Rs have gained interest as potential targets to prevent or treat metabolic disorders. These bitter taste receptors are expressed in functionally distinct types of gastrointestinal mucosal cells, including enteroendocrine cells, which, upon stimulation, increase intracellular Ca²⁺ and release signalling molecules that regulate gut chemosensory processes critical for digestion and absorption of nutrients, for neutralization and expulsion of harmful substances, and for metabolic regulation. Expression of Tas2rs/TAS2Rs in gut mucosa is upregulated by high-fat diets, and intraluminal bitter ‘tastants’ affect gastrointestinal functions and ingestive behaviour through local and gut–brain axis signalling. Tas2rs/TAS2Rs are also found in Paneth and goblet cells, which release antimicrobial peptides and glycoproteins, and in tuft cells, which trigger type 2 immune response against parasites, thus providing a direct line of defence against pathogens. This Review will focus on gut Tas2r/TAS2R distribution, signalling and regulation in enteroendocrine cells, supporting their role as chemosensors of luminal content that serve distinct functions as regulators of body homeostasis and immune response.

味道在食物选择中很重要，它由一组不同的受体精心编排，即味道 G 蛋白偶联受体 （GPCR）。味觉 1 受体（小鼠中的 Tas1rs 和人类的 TAS1R;也称为 T1R）检测甜味和鲜味，味觉 2 受体（小鼠中的 Tas2rs 和人类的 TAS2R;也称为 T2R）检测苦味。这些受体也在口外部位表达，包括胃肠道粘膜。Tas2rs/TAS2Rs 作为预防或治疗代谢紊乱的潜在靶标而受到关注。这些苦味受体在功能不同的胃肠道粘膜细胞中表达，包括肠内分泌细胞，在刺激下，它们会增加细胞内的 Ca²⁺ 并释放调节肠道化学感应过程的信号分子，这些信号分子对营养物质的消化和吸收、有害物质的中和和排出以及代谢调节至关重要。高脂肪饮食上调了肠粘膜中 Tas2rs/TAS2Rs 的表达，腔内苦味“味觉”通过局部和肠脑轴信号传导影响胃肠道功能和摄入行为。Tas2rs/TAS2R 也存在于释放抗菌肽和糖蛋白的潘氏细胞和杯状细胞中，以及触发针对寄生虫的 2 型免疫反应的簇状细胞中，从而提供针对病原体的直接防御线。本综述将重点关注肠道 Tas2r/TAS2R 在肠内分泌细胞中的分布、信号传导和调节，支持它们作为管腔内容物化学传感器的作用，作为身体稳态和免疫反应的调节剂发挥不同的功能。