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.

口腔外苦味受体（Extraoral bitter taste receptors）通过膳食干预调节代谢与肠-脑轴的潜力引人关注。当前学界对这类受体的认知仍较为有限，有关其对衰老影响的相关数据更是匮乏。其高度多样性、低表达水平以及物种依赖性差异所带来的复杂性，为我们理解该类受体带来了不小的挑战。本研究采用实时荧光定量PCR（real-time PCR）对四组人类队列中胃肠道黏膜不同区段的多种味觉受体2型家族（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释放情况进行关联分析。结果显示，在所有检测组织中，TAS2R14的表达水平最高；与之相反，TAS2R39、TAS2R38与TAS2R42的表达水平始终较低。研究发现，衰老可上调降结肠中TAS2R4、TAS2R5、TAS2R13、TAS2R20以及胰高血糖素样肽-1（GLP-1）的mRNA表达水平。在Hutu-80细胞中激活TAS2R14可诱导GLP-1分泌，而激活TAS2R5则可调节GLP-1与多肽YY（PYY）的分泌。考虑到味觉受体2型家族激动剂可能在胃肠道（gastrointestinal tract, GIT）中发生修饰，加之味觉受体2型家族在肠道内独特的表达模式与潜在功能角色，本研究结果表明，采用靶向策略强化特定生理功能以改善健康结局具备可行性。本研究为阐明苦味受体、肠道生理学与潜在膳食干预之间的复杂相互作用提供了宝贵见解。