DataSheet1_Profiling bitter taste receptors (TAS2R) along the gastrointestinal tract and their influence on enterohormone secretion. Gender- and age-related effects in the colon.docx

Extraoral bitter taste receptors offer intriguing potential for modulating metabolism and the gut-brain axis through dietary interventions. Our understanding of these receptors is limited, and data on their effects on ageing are scarce. The complexity conveyed by their high diversity, low expression levels and species-dependent variability challenges our comprehension. We used real-time PCR to examine the relative abundance of multiple TAS2R across different segments of gastrointestinal mucosa in four human cohorts and related them to enteroendocrine secretions at the colon site. TAS2R14 exhibited the highest expression levels in all analyzed tissues. In contrast, TAS2R39, -38 and -42 consistently exhibited lower expression levels. Ageing was found to upregulate TAS2R4, -5, -13, -20 and GLP-1 mRNA in the descending colon. Stimulating TAS2R14 in Hutu-80 cells induced GLP-1 secretion, while stimulating TAS2R5 modulated GLP-1 and PYY secretion. Given the modifications TAS2R agonists may undergo along the GIT, as well as the distinctive expression patterns and possible functional roles of TAS2R receptors along the intestinal tract, our findings suggest the viability of a targeted strategy aimed at enhancing specific functions to improve health outcomes. This study offers valuable insights into the intricate interplay between bitter taste receptors, gut physiology and potential dietary interventions.

口外苦味受体在调节代谢和肠-脑轴通过饮食干预方面展现出诱人的潜力。对这些受体的认识尚显局限，且关于其对衰老影响的数据亦属罕见。其高度多样性、低表达水平及物种依赖性变异所呈现的复杂性，对我们理解构成了挑战。本研究采用实时PCR技术，对四个不同人类队列的胃肠道黏膜不同部位的多种TAS2R的相对丰度进行了检测，并将其与结肠部位的肠内分泌物联系起来。在所有分析的组织中，TAS2R14表现出最高的表达水平。相比之下，TAS2R39、-38和-42则持续展现出较低的表达水平。研究发现，衰老会上调降结肠中TAS2R4、-5、-13、-20和GLP-1 mRNA的表达。刺激Hutu-80细胞中的TAS2R14可诱导GLP-1的分泌，而刺激TAS2R5则可调节GLP-1和PYY的分泌。鉴于TAS2R激动剂在胃肠道中的变化、TAS2R受体沿肠道特异的表达模式及其可能的生理功能，我们的研究结果提示了针对特定功能以提高健康结果的靶向策略的可行性。本研究为苦味受体、肠道生理学及潜在饮食干预之间的复杂相互作用提供了宝贵的见解。