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

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Background/objectivesChronic 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.MethodsA 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.ResultsWhole-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 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 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 ConclusionsMn 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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