Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson's Disease.
Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson's Disease.
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DOI：
10.3390/metabo11010029
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发表时间：
2021-01-04
期刊：
影响因子：
4.1
通讯作者：
Labrie V
中科院分区：
文献类型：
--
作者：
Li P;Killinger BA;Ensink E;Beddows I;Yilmaz A;Lubben N;Lamp J;Schilthuis M;Vega IE;Woltjer R;Pospisilik JA;Brundin P;Brundin L;Graham SF;Labrie V
肠道微生物组可以影响大脑健康，并在帕金森病（PD）中发生改变。阑尾是盲肠中的淋巴组织，涉及肠道微生物群的储存和调节。我们试图确定阑尾微生物组是否在PD中改变，并分析微生物改变的生物学后果。我们通过元转录组学分析研究了PD患者阑尾中功能性微生物群相对于对照组（n = 12 PD，16 C）的变化。我们发现微生物生态失调影响脂质代谢，包括上调负责二级胆汁酸合成的细菌。然后，我们定量测量相对于对照组的阑尾（n = 15 PD，12 C）和回肠（n = 20 PD，20 C）中PD中胆汁酸丰度的变化。PD阑尾中的胆汁酸分析显示疏水性和二级胆汁酸、脱氧胆酸（DCA）和石胆酸（LCA）增加。阑尾和回肠中的进一步蛋白质组学和转录组学分析证实了这些发现，突出了与胆汁酸控制中断一致的PD肠道变化，包括胆固醇稳态和脂质代谢介质的改变。微生物来源的毒性胆汁酸在PD中升高，这表明胆道异常可能在PD发病机制中起作用。
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.
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DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
15.9
作者：
Johnson ME;Stecher B;Labrie V;Brundin L;Brundin P
通讯作者：
Brundin P
影响因子：
4.6
作者：
Hsueh PT;Lin HH;Liu CL;Ni WF;Chen YL;Chen YS
通讯作者：
Chen YS
影响因子：
4.3
作者：
Kaur, Harrisham;Bose, Chandrani;Mande, Sharmila S.
通讯作者：
Mande, Sharmila S.
影响因子：
29.4
作者：
Alemi F;Poole DP;Chiu J;Schoonjans K;Cattaruzza F;Grider JR;Bunnett NW;Corvera CU
通讯作者：
Corvera CU