{"doi":"10.1172/jci147822","title":"Iron deficiency linked to altered bile acid metabolism promotes Helicobacter pylori–induced inflammation–driven gastric carcinogenesis","abstract":"Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions. Mechanistically, these phenotypes were not driven by alterations in the gastric microbiota; however, discovery-based and targeted metabolomics revealed that bile acids were significantly altered in H. pylori-infected mice with iron deficiency, with significant upregulation of deoxycholic acid (DCA), a carcinogenic bile acid. The severity of gastric injury was further augmented when H. pylori-infected mice were treated with DCA, and, in vitro, DCA increased translocation of the H. pylori oncoprotein CagA into host cells. Conversely, bile acid sequestration attenuated H. pylori-induced injury under conditions of iron deficiency. To translate these findings to human populations, we evaluated the association between bile acid sequestrant use and gastric cancer risk in a large human cohort. Among 416,885 individuals, a significant dose-dependent reduction in risk was associated with cumulative bile acid sequestrant use. Further, expression of the bile acid receptor transmembrane G protein-coupled bile acid receptor 5 (TGR5) paralleled the severity of carcinogenic lesions in humans. These data demonstrate that increased H. pylori-induced injury within the context of iron deficiency is tightly linked to altered bile acid metabolism, which may promote gastric carcinogenesis.","journal":"Journal of Clinical Investigation","year":2022,"id":237061,"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":63,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":263090,"name":"M. Blanca Piazuelo","orcid":"0000-0002-0000-1324","position":1,"is_corresponding":false},{"id":374375,"name":"Shailja C. Shah","orcid":"0000-0002-2049-9959","position":2,"is_corresponding":false},{"id":859597,"name":"Judith Romero-Gallo","orcid":null,"position":3,"is_corresponding":false},{"id":859598,"name":"Jessica L. Hart","orcid":null,"position":4,"is_corresponding":false},{"id":103461,"name":"Chao Di","orcid":null,"position":5,"is_corresponding":false},{"id":859599,"name":"James D. Carmichael","orcid":null,"position":6,"is_corresponding":false},{"id":265237,"name":"Alberto G. Delgado","orcid":null,"position":7,"is_corresponding":false},{"id":404609,"name":"Alese E. Halvorson","orcid":"0000-0001-6909-4891","position":8,"is_corresponding":false},{"id":260165,"name":"Robert A. Greevy","orcid":"0000-0002-1821-3544","position":9,"is_corresponding":false},{"id":859600,"name":"Lydia E. 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