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帕金森病与短链脂肪酸的肠道-血液屏障功能受损有关。

Parkinson's Disease Is Associated with Impaired Gut-Blood Barrier for Short-Chain Fatty Acids.

机构信息

Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Mov Disord. 2022 Aug;37(8):1634-1643. doi: 10.1002/mds.29063. Epub 2022 May 24.

DOI:10.1002/mds.29063
PMID:35607987
Abstract

BACKGROUND

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.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

肠道微生物产生的短链脂肪酸(SCFAs)在粪便中减少,但在帕金森病(PD)患者的血浆中却反常增加,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

本研究旨在探讨 PD 患者粪便和血浆中 SCFA 的同步变化,以便秘为混杂因素,更好地厘清与 PD 相关的 SCFA 代谢变化。

方法

采用液相色谱-串联质谱法和气相色谱-质谱法分别检测 33 名健康对照者和 95 名 PD 患者的粪便和血浆 SCFA 浓度。将 PD 患者分为无便秘 PD 患者(n=35)和便秘 PD 患者(n=60)。通过血浆/粪便 SCFA 浓度比值和粪便 α1-抗胰蛋白酶浓度评估肠-血屏障(GBB)通透性。

结果

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。与无便秘 PD 患者相比,便秘 PD 患者粪便中乙酸、异丁酸和异戊酸降低,血浆中乙酸和丙酸升高。便秘加重了 PD 患者的 GBB 通透性。联合粪便和血浆 SCFA 可区分 PD 患者和健康对照者。除丙酸外,粪便 SCFA 与疾病严重程度呈负相关,而血浆乙酸、丙酸和缬草酸呈正相关。

结论

本研究显示 PD 患者粪便和血浆 SCFA 发生改变,与 GBB 受损有关,且可能因便秘而加重。

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