{"doi":"10.3390/metabo15070487","title":"Exploratory Metabolomic and Lipidomic Profiling in a Manganese-Exposed Parkinsonism-Affected Population in Northern Italy","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.","journal":"Metabolites","year":2025,"id":570552,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5335,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1437552,"name":"Daniel Shoieb","orcid":null,"position":1,"is_corresponding":false},{"id":696649,"name":"Somaiyeh Azmoun","orcid":"0000-0003-4951-614X","position":2,"is_corresponding":false},{"id":291145,"name":"Elena Colicino","orcid":"0000-0002-1875-8448","position":3,"is_corresponding":false},{"id":641702,"name":"Yan Jin","orcid":"0000-0001-7075-0366","position":4,"is_corresponding":false},{"id":1038685,"name":"Jinhua Chi","orcid":null,"position":5,"is_corresponding":false},{"id":1437079,"name":"Hari Krishnan Krishnamurthy","orcid":"0000-0002-7832-8423","position":6,"is_corresponding":false},{"id":275019,"name":"Donatella Placidi","orcid":"0000-0003-1606-5397","position":7,"is_corresponding":false},{"id":241692,"name":"Alessandro Padovani","orcid":"0000-0002-0119-3639","position":8,"is_corresponding":false},{"id":233019,"name":"Andrea Pilotto","orcid":"0000-0003-2029-6606","position":9,"is_corresponding":false},{"id":501513,"name":"Fulvio Pepe","orcid":"0009-0002-6437-1110","position":10,"is_corresponding":false},{"id":1476140,"name":"Marinella Tula","orcid":null,"position":11,"is_corresponding":false},{"id":502266,"name":"Patrizia Crippa","orcid":null,"position":12,"is_corresponding":false},{"id":865626,"name":"Xuexia Wang","orcid":"0000-0002-0613-2608","position":13,"is_corresponding":false},{"id":331095,"name":"Haiwei Gu","orcid":"0000-0002-7598-5022","position":14,"is_corresponding":false},{"id":275023,"name":"Roberto G. Lucchini","orcid":"0000-0002-9723-0237","position":15,"is_corresponding":false},{"id":1202099,"name":"Freeman Lewis","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:07.857542Z","pmid":"40710587","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}