Exploratory Metabolomic and Lipidomic Profiling in a Manganese-Exposed Parkinsonism-Affected Population in Northern Italy.

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites Pub Date : 2025-07-20 DOI:10.3390/metabo15070487

Freeman Lewis, Daniel Shoieb, Somaiyeh Azmoun, Elena Colicino, Yan Jin, Jinhua Chi, Hari Krishnamurthy, Donatella Placidi, Alessandro Padovani, Andrea Pilotto, Fulvio Pepe, Marinella Tula, Patrizia Crippa, Xuexia Wang, Haiwei Gu, Roberto Lucchini

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引用次数: 0

Abstract

Background/objectives: Chronic manganese (Mn) exposure is a recognized environmental contributor to Parkinsonian syndromes, including Mn-induced Parkinsonism (MnIP). This study aimed to evaluate whole-blood Mn levels and investigate disease/exposure-status-related alterations in metabolomic and lipidomic profiles.

Methods: A case-control study (N = 97) was conducted in Brescia, Italy, stratifying participants by Parkinsonism diagnosis and residential Mn exposure. Whole-blood Mn was quantified using ICP-MS. Untargeted metabolomic and lipidomic profiling was conducted using LC-MS. Statistical analyses included Mann-Whitney U tests, conditional logistic regression, ANCOVA, and pathway analysis.

Results: Whole-blood Mn levels were significantly elevated in Parkinsonism cases vs. controls (median: 1.55 µg/dL [IQR: 0.75] vs. 1.02 µg/dL [IQR: 0.37]; p = 0.001), with Mn associated with increased odds of Parkinsonism (OR = 2.42, 95% CI: 1.13-5.17; p = 0.022). The disease effect metabolites included 3-sulfoxy-L-tyrosine (β = 1.12), formiminoglutamic acid (β = 0.99), and glyoxylic acid (β = 0.83); all FDR p < 0.001. The exposure effect was associated with elevated glycocholic acid (β = 0.51; FDR p = 0.006) and disrupted butanoate (Impact = 0.03; p = 0.004) and glutamate metabolism (p = 0.03). Additionally, SLC-mediated transmembrane transport was enriched (p = 0.003). The interaction effect identified palmitelaidic acid (β = 0.30; FDR p < 0.001), vitamin B6 metabolism (Impact = 0.08; p = 0.03), and glucose homeostasis pathways. In lipidomics, triacylglycerols and phosphatidylethanolamines were associated with the disease effect (e.g., TG(16:0_10:0_18:1), β = 0.79; FDR p < 0.01). Ferroptosis and endocannabinoid signaling were enriched in both disease and interaction effects, while sphingolipid metabolism was specific to the interaction effect.

Conclusions: Mn exposure and Parkinsonism are associated with distinct metabolic and lipidomic perturbations. These findings support the utility of omics in identifying environmentally linked Parkinsonism biomarkers and mechanisms.

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意大利北部锰暴露的帕金森病患者人群的代谢组学和脂质组学分析

背景/目的：慢性锰（Mn）暴露是公认的帕金森综合征（包括Mn诱导的帕金森病（MnIP））的环境因素。本研究旨在评估全血锰水平，并调查代谢组学和脂质组学特征中疾病/暴露状态相关的改变。方法：在意大利布雷西亚进行了一项病例对照研究（N = 97），根据帕金森病诊断和居住锰暴露对参与者进行分层。采用ICP-MS定量全血Mn。使用LC-MS进行非靶向代谢组学和脂质组学分析。统计分析包括Mann-Whitney U检验、条件logistic回归、ANCOVA和通路分析。结果：与对照组相比，帕金森病患者全血Mn水平显著升高(中位数：1.55µg/dL [IQR: 0.75] vs. 1.02µg/dL [IQR: 0.37]；p = 0.001)， Mn与帕金森病的发病率增加相关(OR = 2.42, 95% CI: 1.13-5.17；P = 0.022)。致病性代谢物包括3-亚砜- l -酪氨酸（β = 1.12）、甲酰基氨基谷氨酸（β = 0.99）、乙醛酸（β = 0.83）；所有FDR p < 0.001。暴露效应与糖胆酸升高相关(β = 0.51；FDR p = 0.006)和破坏丁酸酯(Impact = 0.03；P = 0.004)和谷氨酸代谢（P = 0.03）。此外，slc介导的跨膜运输富集（p = 0.003）。互作效应鉴定棕榈酸(β = 0.30；FDR p < 0.001)，维生素B6代谢(影响= 0.08；P = 0.03)和葡萄糖稳态途径。在脂质组学中，甘油三酯和磷脂酰乙醇胺与疾病效果相关(例如，TG(16:0_10:0_18:1), β = 0.79；FDR p < 0.01)。铁下垂和内源性大麻素信号在疾病和相互作用中都是富集的，而鞘脂代谢是相互作用作用所特有的。结论：锰暴露和帕金森病与不同的代谢和脂质紊乱有关。这些发现支持了组学在识别与环境相关的帕金森病生物标志物和机制方面的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

5.70

自引率

7.30%

发文量

1070

审稿时长

17.17 days

期刊介绍： Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.