The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alterations. We investigated the changes in the functional microbiota in the appendix of PD patients relative to controls (n = 12 PD, 16 C) by metatranscriptomic analysis. We found microbial dysbiosis affecting lipid metabolism, including an upregulation of bacteria responsible for secondary bile acid synthesis. We then quantitatively measure changes in bile acid abundance in PD relative to the controls in the appendix (n = 15 PD, 12 C) and ileum (n = 20 PD, 20 C). Bile acid analysis in the PD appendix reveals an increase in hydrophobic and secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA). Further proteomic and transcriptomic analysis in the appendix and ileum corroborated these findings, highlighting changes in the PD gut that are consistent with a disruption in bile acid control, including alterations in mediators of cholesterol homeostasis and lipid metabolism. Microbially derived toxic bile acids are heightened in PD, which suggests biliary abnormalities may play a role in PD pathogenesis.

中文翻译：

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肠道菌群失调与帕金森氏病中胆汁酸升高有关

肠道微生物组会影响大脑健康，并会改变帕金森氏病（PD）。mi状阑尾是盲肠中的淋巴样组织，与肠道菌群的储存和调节有关。我们试图确定阑尾微生物组是否在PD中发生了改变，并分析了微生物改变的生物学后果。我们通过转录组分析研究了相对于对照（n = 12 PD，16 C），PD患者阑尾功能性菌群的变化。我们发现微生物营养不良会影响脂质代谢，包括引起次级胆汁​​酸合成的细菌上调。然后，我们定量测量相对于附录（n = 15 PD，12 C）和回肠（n = 10）中的对照，PD中胆汁酸丰度的变化。n = 20 PD，20 C）。PD附录中的胆汁酸分析显示疏水性和仲胆汁酸，脱氧胆酸（DCA）和石胆酸（LCA）有所增加。附录和回肠中进一步的蛋白质组学和转录组学分析证实了这些发现，突显了PD肠道的变化与胆汁酸控制的破坏一致，包括胆固醇稳态和脂质代谢介质的改变。微生物引起的有毒胆汁酸在PD中升高，提示胆汁异常可能在PD发病机理中起作用。