{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:45:59Z","timestamp":1791229559128,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T00:00:00Z","timestamp":1658534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["UH3CA140233"],"award-info":[{"award-number":["UH3CA140233"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2022,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR\u2192BE\u2192EA sequence, oral and esophageal microbiota were more diversified, the dominant genus <jats:italic>Streptococcus<\/jats:italic> was progressively depleted while six other genera <jats:italic>Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia<\/jats:italic> and <jats:italic>Lautropia<\/jats:italic> progressively enriched. In NC, <jats:italic>Streptococcus<\/jats:italic> appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll\u2010like and NOD\u2010like receptors, nitrate\u2010nitrite\u2010nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR\u2010BE\u2010EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis.<\/jats:p>","DOI":"10.1002\/ijc.34191","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T06:14:00Z","timestamp":1656137640000},"page":"1703-1716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Progressive dysbiosis of human orodigestive microbiota along the sequence of gastroesophageal reflux, Barrett's esophagus and esophageal adenocarcinoma"],"prefix":"10.1002","volume":"151","author":[{"given":"Yuhan","family":"Hao","sequence":"first","affiliation":[{"name":"Department of Pathology NYU School of Medicine  New York New York USA"},{"name":"Department of Biology, Center for Genomics and Systems Biology New York University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulas","family":"Karaoz","sequence":"additional","affiliation":[{"name":"Earth and Environmental Sciences Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine NYU School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Yachimski","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhi","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Pathology NYU School of Medicine  New York New York USA"},{"name":"Amherst College  Amherst Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos W.","family":"Nossa","sequence":"additional","affiliation":[{"name":"Department of Medicine NYU School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengkao","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Medicine NYU School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Poles","sequence":"additional","affiliation":[{"name":"Department of Medicine NYU School of Medicine  New York New York USA"},{"name":"Department of Veterans Affairs New York Harbor Healthcare System  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Francois","sequence":"additional","affiliation":[{"name":"Department of Medicine NYU School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris","family":"Traube","sequence":"additional","affiliation":[{"name":"Department of Medicine NYU School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Cell Biology NYU School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-0890","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Population Health NYU School of Medicine  New York New York USA"},{"name":"Department of Environmental Medicine NYU School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manolito","family":"Torralba","sequence":"additional","affiliation":[{"name":"The J. 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