{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:23:30Z","timestamp":1793330610543,"version":"4.5.0"},"reference-count":54,"publisher":"BMJ","issue":"10","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2017,7,15]]},"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Helicobacter pylori<\/jats:italic>\n                      is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      to in vivo carcinogenic microenvironments results in genetic modification important for disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      Whole genome sequencing of genetically related\n                      <jats:italic>H. pylori<\/jats:italic>\n                      strains that differ in virulence and targeted\n                      <jats:italic>H. pylori<\/jats:italic>\n                      sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference\n                      <jats:italic>H. pylori<\/jats:italic>\n                      genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within\n                      <jats:italic>fur<\/jats:italic>\n                      (FurR88H). To investigate the direct role of low iron and\/or high salt,\n                      <jats:italic>H. pylori<\/jats:italic>\n                      was continuously cultured\n                      <jats:italic>in vitro<\/jats:italic>\n                      under low iron or high salt conditions to assess\n                      <jats:italic>fur<\/jats:italic>\n                      genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5\u2009days. To extend these results,\n                      <jats:italic>fur<\/jats:italic>\n                      was sequenced in 339 clinical\n                      <jats:italic>H. pylori<\/jats:italic>\n                      strains. Among the isolates examined, 17% (40\/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6\/107) of strains from patients with non-atrophic gastritis alone (p=0.0034).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These results indicate that specific genetic variation arises within\n                      <jats:italic>H. pylori<\/jats:italic>\n                      strains during in vivo adaptation to conditions conducive for gastric carcinogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2017-313863","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T20:50:22Z","timestamp":1505767822000},"page":"1793-1804","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Pan-genomic analyses identify key\n                    <i>Helicobacter pylori<\/i>\n                    pathogenic loci modified by carcinogenic host microenvironments"],"prefix":"10.1136","volume":"67","author":[{"given":"Jennifer M","family":"Noto","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Chopra","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, 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Murdoch, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shay","family":"Leary","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber C","family":"Beckett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith T","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"},{"name":"Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, 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