PDF(Pubmed)
Abstract：
In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson\'s disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota and hosts numerous compounds with immune- and neuromodulating properties. This broad narrative review presents data supporting the concept that microbiota, the Trp-kynurenine (KYN) pathway and aryl hydrocarbon receptors (AhRs) form a triad involved in PD. A disturbed gut-brain axis allows the bidirectional spread of pro-inflammatory molecules and α-synuclein, which may contribute to the development/progression of the disease. We suggest that the peripheral levels of kynurenines and AhR ligands are strongly linked to the Trp metabolism in the gut and should be studied together with the composition of the microbiota. Such an approach can clearly delineate the sub-populations of PD patients manifesting with a disturbed microbiota-Trp-KYN-brain triad, who would benefit from modifications in the Trp metabolism. Analyses of the microbiome, Trp-KYN pathway metabolites and AhR signaling may shed light on the mechanisms of intestinal distress and identify new targets for the diagnosis and treatment in early-stage PD. Therapeutic interventions based on the combination of a well-defined food regimen, Trp and probiotics seem of potential benefit and require further experimental and clinical research.
摘要：
在寿命稳步增长的时代，老年人的神经退行性疾病提出了重大的治疗和社会经济挑战。适当平衡的饮食和微生物组多样性作为神经变性治疗干预的目标越来越受到关注。微生物群可能会影响认知功能，神经元的生存和死亡，在帕金森病（PD）中发现了肠道菌群失调。色氨酸(Trp),必需氨基酸,被微生物群降解，并拥有许多具有免疫和神经调节特性的化合物。这篇广泛的叙述性综述提供了支持微生物群概念的数据，Trp-犬尿氨酸（KYN）途径和芳香烃受体（AhRs）形成参与PD的三联体。受干扰的肠-脑轴允许促炎分子和α-突触核蛋白的双向扩散，这可能有助于疾病的发展/进展。我们建议犬尿氨酸和AhR配体的外周水平与肠道中的Trp代谢密切相关，应与微生物群的组成一起研究。这种方法可以清楚地描绘PD患者的亚群，表现为微生物群-Trp-KYN-脑三联症，谁将受益于Trp代谢的改变。微生物组分析，Trp-KYN通路代谢产物和AhR信号可能揭示肠道窘迫的机制，并为早期PD的诊断和治疗提供新的靶点。基于明确定义的食物方案的组合的治疗干预措施，Trp和益生菌似乎有潜在的益处，需要进一步的实验和临床研究。
