基于代谢组学的味觉异常分子机制的研究

The sense of taste plays a key role in supporting nutritional, metabolic, and preventive health in humans. Ageusia (loss of taste) and hypogeusia (partial loss of taste) are believed to relate to nerve damages and use of certain medications. In contrast, little has been known about the cause of dysgeusia (alteration of taste), which includes taste distortion and phantom taste, and the occurrence of dysgeusia has yet to be shown to be the “primary symptom” of any specific diseases; to date, the molecular mechanism of dysgeusia still remains underexplored. The study presented herein proposes the use of HPLC-ESI-Q-TOF in non-targeted metabolomic analysis of saliva from patients with cacogeusia (constant bitter taste or metallic taste in the mouth), aiming to pin down the metabolites that are common within the dysgeusia patients and differential between the patients and healthy controls. To further investigate the molecular mechanism of dysgeusia, calcium flux assays will be adopted to assess the ability of the identified high-concentration metabolites in activating hT2Rs (human bitter taste receptors) in vitro and to measure the corresponding thresholds of hT2R activation. The proposed study integrates technical approaches of multiple research fields in unraveling the molecular mechanism of dysgeusia and providing implications to current medical challenges. Results of the study will not only blaze a new trail for future metabolomics research, but to give new insights and strategies into the diagnosis and treatment of taste dysfunction.

味觉在人类的营养、心理、危害预防等多个层面中均扮演着重要的角色。味觉的减退及丧失目前已知可能与神经损伤和药物使用等生理状态有关；然而，口中持续感到某种特殊味觉、味觉倒错或味觉失真等“味觉异常”的状况，至今仍无法明确是否为特定疾病或病灶的“必发症状”，也未曾有探讨其分子机制的科学报导。本研究利用高效液相色谱串联电喷雾四级杆飞行时间质谱技术，对主诉为口苦的口腔疾病患者进行非靶向唾液代谢组学分析，挖掘味觉异常所对应的“共性代谢物”、找出味觉异常患者与健康对照组所对应的“差异性代谢物”，并进一步针对辨认出的高浓度交集代谢物进行体外钙流检测，找出能激活苦味受体的唾液代谢物，并测定其对苦味受体的激活阈值，以明确味觉异常的分子基础及其可能的病理机制。本研究以临床问题为核心，整合多学科研究手段，不仅有望揭示味觉异常的分子机制，并能为代谢组学研究开拓了新的研究方向，也为味觉障碍的临床诊治提供新的靶点与思路。

味觉在人类的营养、心理、危害预防等多个层面扮演着重要的角色。本研究利用高效液相色谱串联电喷雾四级杆飞行时间质谱技术，分析味觉异常及灼口综合症患者的唾液代谢组学，试图探索味觉相关疾病的共性代谢物，以及相对于健康对照组的差异性代谢物，期望揭示味觉相关疾病的其分子机制。实际操作后发现，本研究在临床阶段遭遇病人筛选不易、唾液样本质量控管困难等问题，加上检测阶段色质谱仪器稳定度不佳，严重影响分析结果的准确度。为改善唾液样本的质量问题，本研究进一步探讨了使用石墨烯对样本进行预处理的可行性。经实验证明，石墨烯能有效去除唾液样本中的蛋白质，但无法吸附唾液样本中的塩离子。本研究重新审视了当前代谢组学分析方法用于临床检测的可行性，指出此领域仍需解决的问题点，并提供了新的样本预处理方法，为代谢组学研究开拓了新的研究思路。