{"doi":"10.1016/j.ecoenv.2025.118654","title":"Diesel exhaust induces gut microbiome dysbiosis and reduced fecal acetate: Role of acetate supplementation","abstract":"Air pollution exposure enhances the risk of cardiovascular morbidity and mortality. Epidemiological studies provide strong evidence of a link between exposure to ambient particulate matter with aerodynamic diameter< 2.5 µm (PM 2.5 ) and development of cardiovascular and metabolic disorders. We have shown that inhaled ultrafine particles (UFP) or whole diesel exhaust (DE), enriched in UFP, induce cardiometabolic effects, including dyslipidemia and hepatic steatosis. However, the pathogenic mechanisms remain unknown. We recently demonstrated that exposure to ambient particulate in the ultrafine-size range altered the gut microbiota composition in various animal models, with a potential to induce systemic effects. Thus, we hypothesized that sub-chronic inhalation exposure to DE leads to gut dysbiosis and altered gut-derived metabolites, likely responsible for some of the metabolic effects. Male apolipoprotein E -/- (ApoE -/- ) mice, exposed to inhaled DE vs. filtered air (FA) (6 h/day, 5 days/week for 16 weeks) displayed alterations in cecal microbiota composition, which associated with elevated plasma cholesterol and triglycerides, as well as hepatic triglycerides and oxidized lipids. DE exposure upregulated hepatic mRNA and protein levels of 12-lipoxygenase (Alox12), together with significantly reduced fecal acetate levels, correlating with changes in lipids and cecal microbiota composition. Metabolic effects were recapitulated in HepG2 cells treated with DE particles, including elevated Alox12 mRNA levels and decreased respiration in isolated mitochondria. Supplementation with gut-derived short chain fatty acid acetate reversed these effects in cells. In conclusion, inhaled DE induced gut microbiome dysbiosis, lipid peroxidation and triglyceride accumulation, likely via mitochondrial dysfunction, which was rescued in cells by acetate supplementation.","journal":"Ecotoxicology and Environmental Safety","year":2025,"id":524046,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":1040722,"name":"Candace Chang","orcid":"0000-0002-1568-7648","position":1,"is_corresponding":false},{"id":242284,"name":"Laurent Vergnes","orcid":"0000-0002-8804-589X","position":2,"is_corresponding":false},{"id":1076474,"name":"Dawoud Sulaiman","orcid":null,"position":3,"is_corresponding":false},{"id":1286304,"name":"Fen Yin","orcid":null,"position":4,"is_corresponding":false},{"id":701612,"name":"James A. Stewart","orcid":"0000-0001-8920-8809","position":5,"is_corresponding":false},{"id":236693,"name":"Margarete Mehrabian","orcid":"0000-0002-8569-8852","position":6,"is_corresponding":false},{"id":266060,"name":"Joel D. Kaufman","orcid":"0000-0003-4174-9037","position":7,"is_corresponding":false},{"id":36336,"name":"Jonathan P. Jacobs","orcid":"0000-0003-4698-0254","position":8,"is_corresponding":false},{"id":15457,"name":"Aldons J. Lusis","orcid":"0000-0001-9013-0228","position":9,"is_corresponding":false},{"id":242287,"name":"Karen Reue","orcid":"0000-0002-7487-2624","position":10,"is_corresponding":false},{"id":1285880,"name":"Michael E. Rosenfeld","orcid":"0000-0003-2784-4345","position":11,"is_corresponding":false},{"id":338793,"name":"Jesús A. Araujo","orcid":"0000-0001-8279-8922","position":12,"is_corresponding":false},{"id":711436,"name":"Rajat Gupta","orcid":"0000-0003-2887-1935","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:50:07.396155Z","pmid":"40763515","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":[]}