{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:18:56Z","timestamp":1790666336934,"version":"4.1.0"},"reference-count":56,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"NIH","award":["P01CA163200"],"award-info":[{"award-number":["P01CA163200"]}]},{"name":"NIH","award":["R01DK100405"],"award-info":[{"award-number":["R01DK100405"]}]},{"name":"NIH","award":["P01CA163200"],"award-info":[{"award-number":["P01CA163200"]}]},{"name":"NIH","award":["P30DK41301"],"award-info":[{"award-number":["P30DK41301"]}]},{"name":"NIH","award":["P01CA163200"],"award-info":[{"award-number":["P01CA163200"]}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX001473"],"award-info":[{"award-number":["1I01BX001473"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002135","name":"Hirshberg Foundation for Pancreatic Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002135","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["T32 DK 07180"],"award-info":[{"award-number":["T32 DK 07180"]}]},{"name":"VA Career Development Award","award":["IK2CX001717"],"award-info":[{"award-number":["IK2CX001717"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:p> Pancreatic ductal adenocarcinoma (PDAC)\u2019s growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. In previous work, we have shown that metformin can prevent the increased incidence of PDAC in a Kras<jats:sup>G12D<\/jats:sup> mouse model subjected to a diet high in fat and calories (HFCD). One potential way that metformin can affect the host is through alterations in the gut microbiome. Therefore, we investigated microbial associations with PDAC development and metformin use in the same mouse model. Lox-Stop-Lox Kras G12D\/+ (LSL-Kras G12D\/+); p48-Cre (KC) mice were given control diet, HFCD, or HFCD with 5 mg\/mL metformin in drinking water for 3 mo. At the end of the 3 mo, 16S rRNA sequencing was performed to characterize microbiome composition of duodenal mucosal, duodenal luminal, and cecal luminal samples. KC mice on an HFCD demonstrated depletion of intact acini and formation of advanced pancreatic intraepithelial neoplasia. This effect was completely abrogated by metformin treatment. HFCD was associated with significant changes in microbial composition and diversity in the duodenal mucosa and lumen, much of which was prevented by metformin. In particular, Clostridium sensu stricto was negatively correlated with percent intact acini and seemed to be inhibited by the addition of metformin while on an HFCD. Administration of metformin eliminated PDAC formation in KC mice. This change was associated with significant microbial changes in both the mucosal and luminal microbiome of the duodenum. This suggests that the microbiome may be a potential mediator of the chemopreventive effects of metformin. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Pancreatic ductal adenocarcinoma (PDAC)\u2019s growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. Administration of metformin eliminated PDAC formation in KC mice with diet-induced obesity. This change was associated with significant microbial changes in both the mucosal and luminal microbiome of the duodenum. This suggests that the microbiome may be a potential mediator of the chemopreventive effects of metformin. <\/jats:p>","DOI":"10.1152\/ajpgi.00170.2019","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T18:59:20Z","timestamp":1569265160000},"page":"G763-G772","source":"Crossref","is-referenced-by-count":43,"title":["Metformin alters the duodenal microbiome and decreases the incidence of pancreatic ductal adenocarcinoma promoted by diet-induced obesity"],"prefix":"10.1152","volume":"317","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0105-8063","authenticated-orcid":false,"given":"Tien S.","family":"Dong","sequence":"first","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Hua","family":"Chang","sequence":"additional","affiliation":[{"name":"CURE: Digestive Diseases Research Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"Department of Surgery, David Geffen School of Medicine at the University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meg","family":"Hauer","sequence":"additional","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"CURE: Digestive Diseases Research Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"University of California Los Angeles Microbiome Center, David Geffen School of Medicine at the University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venu","family":"Lagishetty","sequence":"additional","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"CURE: Digestive Diseases Research Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"University of California Los Angeles Microbiome Center, David Geffen School of Medicine at the University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Katzka","sequence":"additional","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"CURE: Digestive Diseases Research Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"University of California Los Angeles Microbiome Center, David Geffen School of Medicine at the University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Rozengurt","sequence":"additional","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"CURE: Digestive Diseases Research Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"Division of Gastroenterology, Hepatology, and Parenteral Nutrition, Veterans\u2019 Affairs Greater Los Angeles Healthcare System, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"CURE: Digestive Diseases Research Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"University of California Los Angeles Microbiome Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"Division of Gastroenterology, Hepatology, and Parenteral Nutrition, Veterans\u2019 Affairs Greater Los Angeles Healthcare System, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Eibl","sequence":"additional","affiliation":[{"name":"CURE: Digestive Diseases Research Center, David Geffen School of Medicine at the University of California, Los Angeles, California"},{"name":"Department of Surgery, David Geffen School of Medicine at the University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-9993.2001.01070.pp.x."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.09.019"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000131556.22382.3c"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20778"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5233-y"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0498-0"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3869"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8986.1"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.f.303"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3402\/mehd.v26.26191"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24337-8"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184455"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2005.05.007"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-13-0065"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.08.067"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38415.708634.F7"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nature15766"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5043"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.06.037"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00309-X"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200105000-00003"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800685"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602619"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2016.1257469"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000010036"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0418"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e31827aec40"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27965-2"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01357-14"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06207-x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00111.x"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.10.005"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114573"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-1-257"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2329"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2015.16"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-407863-5.00018-6"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-1134"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0155"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206366"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.04.001"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303839"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.11.010"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1027"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057289"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1530509100"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im0741s107"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0000000000001130"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/nature05414"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.13732"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1159\/000493214"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2014.04.007"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4345"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.21.1586"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nature12347"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15692"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00170.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T07:19:58Z","timestamp":1574493598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00170.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,1]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12,1]]}},"alternative-id":["10.1152\/ajpgi.00170.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00170.2019","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,1]]}}}