{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:42:24Z","timestamp":1791999744213,"version":"4.4.0"},"reference-count":89,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA158319"],"award-info":[{"award-number":["R01CA158319"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:p>\n                    The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett\u2019s esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome\u2013esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 \u03bcg\/rat\/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR\/NF-\u03baB\/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (\n                    <jats:italic>Streptococcus parasanguinis<\/jats:italic>\n                    ,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , and\n                    <jats:italic>Proteus mirabilis<\/jats:italic>\n                    ). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including\n                    <jats:italic>Ccl4<\/jats:italic>\n                    ,\n                    <jats:italic>Cd14<\/jats:italic>\n                    ,\n                    <jats:italic>Crp<\/jats:italic>\n                    ,\n                    <jats:italic>Cxcl1<\/jats:italic>\n                    ,\n                    <jats:italic>Il6<\/jats:italic>\n                    ,\n                    <jats:italic>Il1b<\/jats:italic>\n                    ,\n                    <jats:italic>Lbp<\/jats:italic>\n                    ,\n                    <jats:italic>Lcn2<\/jats:italic>\n                    ,\n                    <jats:italic>Myd88<\/jats:italic>\n                    ,\n                    <jats:italic>Nfkb1<\/jats:italic>\n                    ,\n                    <jats:italic>Tlr2<\/jats:italic>\n                    , and\n                    <jats:italic>Tlr4<\/jats:italic>\n                    , aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.168112","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T19:19:50Z","timestamp":1707851990000},"source":"Crossref","is-referenced-by-count":13,"title":["Prebiotic proanthocyanidins inhibit bile reflux\u2013induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-5391","authenticated-orcid":true,"given":"Katherine M.","family":"Weh","sequence":"first","affiliation":[{"name":"Department of Surgery, Section of Thoracic Surgery, and"},{"name":"Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor L.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Thoracic Surgery, and"},{"name":"Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Thoracic Surgery, and"},{"name":"Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget A.","family":"Tripp","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Statistics, Department of Food Science Technology, Quantitative Life Sciences Initiative, University of Nebraska-Lincoln, Lincoln, Nebraska, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy B.","family":"Howell","sequence":"additional","affiliation":[{"name":"Marucci Center for Blueberry and Cranberry Research, Rutgers University, Chatsworth, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H.","family":"Rubenstein","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"LTC Charles S. Kettles Veterans Affairs Medical Center, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian A.","family":"Abrams","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Westerhoff","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Kresty","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Thoracic Surgery, and"},{"name":"Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00419-3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2013.06.005"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.08.044"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2018.02.004"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305997"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14895"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1177\/2042098613482484"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.7193"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315306"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310376"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.791274"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s11938-018-0171-5"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-19-0008"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9081764"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34191"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00951-6"},{"key":"B17","doi-asserted-by":"crossref","unstructured":"Solfisburg QS, et al. 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