{"doi":"10.1038/s42003-021-02898-1","title":"Cadmium exposure modulates the gut-liver axis in an Alzheimer’s disease mouse model","abstract":"The human Apolipoprotein E4 (ApoE4) variant is the strongest known genetic risk factor for Alzheimer's disease (AD). Cadmium (Cd) has been shown to impair learning and memory at a greater extent in humanized ApoE4 knock-in (ApoE4-KI) mice as compared to ApoE3 (common allele)-KI mice. Here, we determined how cadmium interacts with ApoE4 gene variants to modify the gut-liver axis. Large intestinal content bacterial 16S rDNA sequencing, serum lipid metabolomics, and hepatic transcriptomics were analyzed in ApoE3- and ApoE4-KI mice orally exposed to vehicle, a low dose, or a high dose of Cd in drinking water. ApoE4-KI males had the most prominent changes in their gut microbiota, as well as a predicted down-regulation of many essential microbial pathways involved in nutrient and energy homeostasis. In the host liver, cadmium-exposed ApoE4-KI males had the most differentially regulated pathways; specifically, there was enrichment in several pathways involved in platelet activation and drug metabolism. In conclusion, Cd exposure profoundly modified the gut-liver axis in the most susceptible mouse strain to neurological damage namely the ApoE4-KI males, evidenced by an increase in microbial AD biomarkers, reduction in energy supply-related pathways in gut and blood, and an increase in hepatic pathways involved in inflammation and xenobiotic biotransformation.","journal":"Communications Biology","year":2021,"id":170480,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":703329,"name":"Megumi Matsushita","orcid":"0000-0002-6874-0836","position":1,"is_corresponding":false},{"id":703330,"name":"Liang Zhang","orcid":"0000-0002-1720-9287","position":2,"is_corresponding":false},{"id":703331,"name":"Hao Wang","orcid":"0000-0002-0901-5183","position":3,"is_corresponding":false},{"id":331094,"name":"Xiaojian Shi","orcid":"0000-0001-7456-2901","position":4,"is_corresponding":false},{"id":331095,"name":"Haiwei Gu","orcid":"0000-0002-7598-5022","position":5,"is_corresponding":false},{"id":704135,"name":"Zhengui Xia","orcid":null,"position":6,"is_corresponding":false},{"id":342633,"name":"Julia Yue Cui","orcid":"0000-0002-8564-1784","position":7,"is_corresponding":false},{"id":422498,"name":"Angela Zhang","orcid":"0000-0002-4953-982X","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T23:46:24.040760Z","pmid":"34912029","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":[]}