Parkinson's Disease Is Associated with Impaired Gut–Blood Barrier for Short‐Chain Fatty Acids
Parkinson's Disease Is Associated with Impaired Gut–Blood Barrier for Short‐Chain Fatty Acids
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帕金森病与短链脂肪酸肠道血屏障受损有关
DOI：
10.1002/mds.29063
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Qin Xiao
中科院分区：
文献类型：
--
作者：
Xiaodong Yang;Penghui Ai;Xiaoqin He;Chengjun Mo;Yi Zhang;Shaoqing Xu;Yiqiu Lai;Yiwei Qian;Qin Xiao
帕金森病（PD）患者肠道菌群产生的短链脂肪酸（SCFAs）在粪便中减少，但在血浆中却矛盾地增加，这可能源于肠壁渗漏。在进行微生物代谢物研究时，应考虑肠道功能。目的是研究PD患者粪便和血浆中SCFA的同步变化，以便秘为混杂因素，更好地解开与PD相关的SCFA代谢。采用液相色谱质谱法和气相色谱质谱法分别测定了33名健康对照者和95名PD患者粪便和血浆中SCFAs的浓度。PD患者分为PD不伴便秘患者（n = 35）和PD伴便秘患者（n = 60）。采用血浆/粪便SCFA浓度比和粪便α1-抗胰蛋白酶浓度评估肠-血屏障（GBB）通透性。PD患者粪便中乙酸、丙酸和丁酸浓度降低，血浆中乙酸和丙酸浓度升高。便秘PD患者粪乙酸、异丁酸和异戊酸较低，血浆乙酸和丙酸高于无便秘PD患者。便秘加重PD患者GBB通透性。粪便和血浆SCFAs联合使用可将PD患者与健康对照者区分开来。除丙酸外，粪便SCFAs与疾病严重程度呈负相关，而血浆乙酸、丙酸和戊酸呈正相关。我们的研究显示PD患者粪便和血浆SCFAs的改变与GBB受损有关，并且可能因便秘而加重。©2022国际帕金森和运动障碍学会。
Short-chain fatty acids (SCFAs) produced by gut microbiota are reduced in feces but paradoxically increased in plasma of patients with Parkinson's disease (PD), which may stem from intestinal wall leakage. Gut function should be taken into consideration when conducting microbial-metabolite research.The objective was to investigate synchronous changes of SCFAs in feces and plasma of patients with PD, taking constipation as a confounder to better disentangle the SCFA metabolism exclusively associated with PD.The concentrations of fecal and plasma SCFAs in 33 healthy control subjects and 95 patients with PD were measured using liquid and gas chromatography mass spectrometry, respectively. Patients with PD were divided into patients with PD without constipation (n = 35) and patients with PD with constipation (n = 60). Gut-blood barrier (GBB) permeability was assessed by plasma/fecal ratio of SCFA concentrations and fecal α1-antitrypsin concentration.Patients with PD displayed decreased concentrations of fecal acetic, propionic, and butyric acid and increased concentrations of plasma acetic and propionic acid. Fecal acetic, isobutyric, and isovaleric acid were lower and plasma acetic and propionic acid were higher in patients with PD with constipation than in patients with PD without constipation. Constipation aggravated GBB permeability in patients with PD. Combined fecal and plasma SCFAs could discriminate patients with PD from healthy control subjects. Fecal SCFAs, except propionic acid, were negatively correlated with disease severity, while plasma acetic, propionic, and valeric acid showed a positive correlation.Our study showed alterations of fecal and plasma SCFAs in patients with PD that were associated with an impaired GBB and might be aggravated by constipation. © 2022 International Parkinson and Movement Disorder Society.
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