Bedarf J R, Hildebrand F, Coelho L P, Sunagawa S, Bahram M, Goeser F, Bork P, Wüllner U
Department of Neurology, University of Bonn, Bonn, Germany.
German Centre for neurodegenerative disease research (DZNE), Bonn, Germany.
Genome Med. 2017 Apr 28;9(1):39. doi: 10.1186/s13073-017-0428-y.
Parkinson's disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, the enteric system with its vast diversity of microorganisms may be involved in PD pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA-naïve PD patients might also serve as a biomarker.
We performed metagenomic shotgun analyses and compared the fecal microbiomes of 31 early stage, L-DOPA-naïve PD patients to 28 age-matched controls.
We found increased Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified Firmicutes, whereas Prevotellaceae (Prevotella copri) and Erysipelotrichaceae (Eubacterium biforme) were markedly lowered in PD samples. The observed differences could reliably separate PD from control with a ROC-AUC of 0.84. Functional analyses of the metagenomes revealed differences in microbiota metabolism in PD involving the ẞ-glucuronate and tryptophan metabolism. While the abundances of prophages and plasmids did not differ between PD and controls, total virus abundance was decreased in PD participants. Based on our analyses, the intake of either a MAO inhibitor, amantadine, or a dopamine agonist (which in summary relates to 90% of PD patients) had no overall influence on taxa abundance or microbial functions.
Our data revealed differences of colonic microbiota and of microbiota metabolism between PD patients and controls at an unprecedented detail not achievable through 16S sequencing. The findings point to a yet unappreciated aspect of PD, possibly involving the intestinal barrier function and immune function in PD patients. The influence of the parkinsonian medication should be further investigated in the future in larger cohorts.
帕金森病（PD）目前被认为是一种蛋白质聚集性疾病，其病理涉及肠道和中枢神经系统，可能通过迷走神经从一个系统传播到另一个系统。由于胃肠功能障碍通常先于运动症状出现或与之并行，具有大量微生物多样性的肠道系统可能参与了PD的发病机制。未经左旋多巴治疗的PD患者肠道微生物分类水平的改变也可能作为一种生物标志物。
我们进行了宏基因组鸟枪法分析，并将31例早期未经左旋多巴治疗的PD患者的粪便微生物群与28例年龄匹配的对照进行了比较。
我们发现疣微菌科（嗜黏蛋白阿克曼氏菌）和未分类的厚壁菌门增加，而普雷沃氏菌科（普氏粪杆菌）和丹毒丝菌科（双形真杆菌）在PD样本中显著降低。观察到的差异能够可靠地将PD与对照区分开来，ROC-AUC为0.84。宏基因组的功能分析揭示了PD患者微生物群代谢在β-葡萄糖醛酸和色氨酸代谢方面的差异。虽然噬菌体和质粒的丰度在PD患者和对照之间没有差异，但PD参与者的总病毒丰度降低。根据我们的分析，服用单胺氧化酶抑制剂、金刚烷胺或多巴胺激动剂（总计涉及90%的PD患者）对分类群丰度或微生物功能没有总体影响。
我们的数据以前所未有的细节揭示了PD患者和对照之间结肠微生物群及其代谢的差异，这是通过16S测序无法实现的。这些发现指出了PD一个尚未被认识的方面，可能涉及PD患者的肠道屏障功能和免疫功能。未来应在更大的队列中进一步研究帕金森病药物的影响。
