{"doi":"10.1016/j.chom.2024.11.012","title":"Intestinal E. coli-produced yersiniabactin promotes profibrotic macrophages in Crohn’s disease","abstract":"Inflammatory bowel disease (IBD)-associated fibrosis causes significant morbidity. Mechanisms are poorly understood but implicate the microbiota, especially adherent-invasive Escherichia coli (AIEC). We previously demonstrated that AIEC producing the metallophore yersiniabactin (Ybt) promotes intestinal fibrosis in an IBD mouse model. Since macrophages interpret microbial signals and influence inflammation/tissue remodeling, we hypothesized that Ybt metal sequestration disrupts this process. Here, we show that macrophages are abundant in human IBD-fibrosis tissue and mouse fibrotic lesions, where they co-localize with AIEC. Ybt induces profibrotic gene expression in macrophages via stabilization and nuclear translocation of hypoxia-inducible factor 1-alpha (HIF-1α), a metal-dependent immune regulator. Importantly, Ybt-producing AIEC deplete macrophage intracellular zinc and stabilize HIF-1α through inhibition of zinc-dependent HIF-1α hydroxylation. HIF-1α+ macrophages localize to sites of disease activity in human IBD-fibrosis strictures and mouse fibrotic lesions, highlighting their physiological relevance. Our findings reveal microbiota-mediated metal sequestration as a profibrotic trigger targeting macrophages in the inflamed intestine.","journal":"Cell Host & Microbe","year":2024,"id":423989,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1219862,"name":"Marlus da Silva Pedrosa","orcid":"0000-0002-4052-7208","position":1,"is_corresponding":false},{"id":270823,"name":"Lacey R. Lopez","orcid":"0000-0002-5667-8107","position":2,"is_corresponding":false},{"id":1149116,"name":"Taylor Tibbs","orcid":"0000-0003-3663-9570","position":3,"is_corresponding":false},{"id":1118702,"name":"Joanna Jeyachandran","orcid":null,"position":4,"is_corresponding":false},{"id":1220323,"name":"Emily Vignieri","orcid":null,"position":5,"is_corresponding":false},{"id":1220324,"name":"Aaron Rothemich","orcid":null,"position":6,"is_corresponding":false},{"id":1220325,"name":"Ian Cumming","orcid":null,"position":7,"is_corresponding":false},{"id":1220326,"name":"Alexander D Irmscher","orcid":null,"position":8,"is_corresponding":false},{"id":1220327,"name":"Corey J Haswell","orcid":null,"position":9,"is_corresponding":false},{"id":346805,"name":"William C. Zamboni","orcid":"0000-0002-8319-4482","position":10,"is_corresponding":false},{"id":1043936,"name":"Yen‐Rei Yu","orcid":"0000-0002-1984-7186","position":11,"is_corresponding":false},{"id":598575,"name":"Melissa Ellermann","orcid":"0000-0002-8942-6889","position":12,"is_corresponding":false},{"id":291505,"name":"Lee A. Denson","orcid":"0000-0001-8045-7198","position":13,"is_corresponding":false},{"id":270825,"name":"Janelle C. Arthur","orcid":"0000-0002-4796-0207","position":14,"is_corresponding":false},{"id":904379,"name":"Ju-Hyun Ahn","orcid":null,"position":0,"is_corresponding":true}],"reference_count":172,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:58:01.889748Z","pmid":"39701098","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":[]}