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TAS2R38 苦味受体基因变异与帕金森病患者肠道微生物群特征相关:一项初步研究。

Genetic variants of TAS2R38 bitter taste receptor associate with distinct gut microbiota traits in Parkinson's disease: A pilot study.

机构信息

Department of Biomedical Sciences, University of Cagliari, Italy.

Department of Neurology AO Brotzu, Cagliari, Italy.

出版信息

Int J Biol Macromol. 2020 Dec 15;165(Pt A):665-674. doi: 10.1016/j.ijbiomac.2020.09.056. Epub 2020 Sep 16.

DOI:10.1016/j.ijbiomac.2020.09.056
PMID:32946938
Abstract

The non-tasting form of the bitter taste receptor, TAS2R38, has been shown as a genetic risk factor associated with the development of Parkinson's disease (PD). Specific taste receptors that are expressed in the lower gastrointestinal tract may respond to alteration in gut microbiota composition, detecting bacterial molecules, and regulate immune responses. Given the importance of brain-gut-microbiota axis and gene-environment interactions in PD, we investigate the associations between the genetic variants of TAS2R38 and gut microbiota composition in 39 PD patients. The results confirm that the majority of PD patients have reduced sensitivity to 6-n-propylthiouracil (PROP) and are carriers of at least one non-functional TAS2R38 AVI haplotype. Moreover, we found this correlation to be associated with a reduction in bacteria alpha-diversity with a predominant reduction of Clostridium genus. We hypothesised that the high frequency of the non-taster form of TAS2R38 associated with a diminuition of Clostridium bacteria in PD might determine a reduction in the activation of protective signalling-molecules useful in preserving gut homeostasis. This pilot study, by identifying a decrease in specific bacteria associated with a reduced sensitivity to PROP, adds essential information that opens new avenues of research into the association of PD microbiota composition and sensory modification.

摘要

苦味受体 TAS2R38 的无味觉形式已被证明是与帕金森病 (PD) 发展相关的遗传风险因素。在下消化道表达的特定味觉受体可能会对肠道微生物群落组成的变化做出反应,检测细菌分子,并调节免疫反应。鉴于脑-肠-微生物群轴和基因-环境相互作用在 PD 中的重要性,我们研究了 39 名 PD 患者中 TAS2R38 基因变异与肠道微生物群落组成之间的关联。结果证实,大多数 PD 患者对 6-正丙基硫氧嘧啶 (PROP) 的敏感性降低,并且至少携带一种无功能的 TAS2R38 AVI 单倍型。此外,我们发现这种相关性与细菌 α-多样性的降低有关,其中主要是梭菌属的减少。我们假设,与 PD 中 Clostridium 细菌减少相关的 TAS2R38 无味觉形式的高频率可能会导致保护性信号分子的激活减少,而这些信号分子对于维持肠道内环境稳态是有用的。这项初步研究通过确定与 PROP 敏感性降低相关的特定细菌的减少,提供了重要信息,为 PD 微生物群落组成和感觉修饰的关联研究开辟了新的途径。

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