{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:01:57Z","timestamp":1790874117518,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T00:00:00Z","timestamp":1521590400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2018.00214","type":"journal-article","created":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T04:30:12Z","timestamp":1521606612000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":74,"title":["Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration"],"prefix":"10.3389","volume":"9","author":[{"given":"Ru","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Xiong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Rong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Dong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1038\/ijo.2015.84","article-title":"The role of short chain fatty acids in appetite regulation and energy homeostasis","volume":"39","author":"Byrne","year":"2015","journal-title":"Int. J. Obesity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s12272-008-1127-4","article-title":"Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine","volume":"31","author":"Chae","year":"2008","journal-title":"Arch. Pharm. Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0304-3835(90)90018-S","article-title":"Berberine-induced morphologic differentiation and down-regulation of c-Ki-ras2 protooncogene expression in human teratocarcinoma cells","volume":"55","author":"Chang","year":"1990","journal-title":"Cancer Lett"},{"key":"B4","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1208\/s12249-011-9632-z","article-title":"Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats","volume":"12","author":"Chen","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"B5","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1007\/s002840010294","article-title":"Effects of acetate and butyrate during glycerol fermentation by Clostridium butyricum","volume":"43","author":"Colin","year":"2001","journal-title":"Curr. Microbiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1517\/14712598.2013.776037","article-title":"Effects of berberine on lipid profile in subjects with low cardiovascular risk","volume":"13","author":"Derosa","year":"2013","journal-title":"Expert Opin. Biol. Ther"},{"key":"B7","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1055\/s-0032-1328321","article-title":"The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials","volume":"79","author":"Dong","year":"2013","journal-title":"Planta Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"12155","DOI":"10.1038\/srep12155","article-title":"Transforming berberine into its intestine-absorbable form by the gut microbiota","volume":"5","author":"Feng","year":"2015","journal-title":"Sci. Rep"},{"key":"B9","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s00253-007-1180-9","article-title":"Transcriptional profile induced by furazolidone treatment of Shigella flexneri","volume":"7","author":"Fu","year":"2007","journal-title":"Appl. Microbiol Biot"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.2337\/db08-1637","article-title":"Butyrate improves insulin sensitivity and increases energy expenditure in mice","volume":"58","author":"Gao","year":"2009","journal-title":"Diabetes"},{"key":"B11","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.jpba.2007.03.022","article-title":"Determination of berberine in human plasma by liquid chromatography\u2013electrospray ionization\u2013mass spectrometry","volume":"44","author":"Hua","year":"2007","journal-title":"J. Pharmaceut. Biomed"},{"key":"B12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S0304-3835(99)00264-5","article-title":"Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines","volume":"148","author":"Iizuka","year":"2000","journal-title":"Cancer Lett"},{"key":"B13","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nm.3145","article-title":"Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis","volume":"19","author":"Koeth","year":"2013","journal-title":"Nat. Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1038\/nm1135","article-title":"Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins","volume":"10","author":"Kong","year":"2004","journal-title":"Nat. Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1097\/MCO.0b013e32835665fa","article-title":"Butyrate: implications for intestinal function","volume":"15","author":"Leonel","year":"2012","journal-title":"Curr. Opin. Clin. Nutr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/1479-5876-9-62","article-title":"Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes","volume":"9","author":"Li","year":"2011","journal-title":"J. Transl. Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"4391","DOI":"10.1002\/jps.21721","article-title":"Oxidative demethylenation and subsequent glucuronidation are the major metabolic pathways of berberine in rats","volume":"98","author":"Liu","year":"2009","journal-title":"J. Pharm. Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1124\/dmd.110.033936","article-title":"Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats","volume":"38","author":"Liu","year":"2010","journal-title":"Drug Metab. Dispos"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4181","DOI":"10.1002\/jps.23718","article-title":"Excretion of berberine and its metabolites in oral administration in rats","volume":"102","author":"Ma","year":"2013","journal-title":"J. Pharm. Sci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1517\/17425255.2.6.875","article-title":"Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction","volume":"2","author":"Martignoni","year":"2006","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1152\/ajpcell.00228.2014","article-title":"From microbe to man: the role of microbial short chain fatty acid metabolites in host cell biology","volume":"307","author":"Natarajan","year":"2014","journal-title":"Am. J. Physiol. Cell. Physiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1124\/dmd.108.021659","article-title":"Isolation and identification of urinary metabolites of berberine in rats and humans","volume":"36","author":"Qiu","year":"2008","journal-title":"Drug Metab. Dispos"},{"key":"B24","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nri.2016.42","article-title":"Gut microbiota, metabolites and host immunity","volume":"16","author":"Rooks","year":"2016","journal-title":"Nat. Rev. Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12917-017-0981-z","article-title":"Raw meat based diet influences faecal microbiome and end products of fermentation in healthy dogs","volume":"13","author":"Sandri","year":"2016","journal-title":"BMC Vet. Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4127","DOI":"10.1128\/JCM.42.9.4127-4129.2004","article-title":"Isolation of metronidazole-resistant bacteroides fragilis carrying the nima nitroreductase gene from a patient in washington state","volume":"42","author":"Schapiro","year":"2004","journal-title":"J. Clin. Microbiol"},{"key":"B27","first-page":"64","article-title":"Studies on the intravenous pharmacokinetics and oral absorption of berberine HCL in beagle dogs","volume":"9","author":"Shen","year":"1993","journal-title":"Chin. Pharmacol. Bull"},{"key":"B28","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1159\/000441768","article-title":"Reduced abundance of butyrate-producing bacteria species in the fecal microbial community in crohn's disease","volume":"93","author":"Takahashi","year":"2016","journal-title":"Digestion"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e77969","DOI":"10.1371\/journal.pone.0077969","article-title":"Tissue distribution of berberine and its metabolites after oral administration in rats","volume":"8","author":"Tan","year":"2013","journal-title":"PLoS ONE"},{"key":"B30","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature11552","article-title":"Functional interactions between the gut microbiota and host metabolism","volume":"489","author":"Tremaroli","year":"2012","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1124\/dmd.32.4.405","article-title":"Hepatobiliary excretion of berberine","volume":"32","author":"Tsai","year":"2004","journal-title":"Drug Metab. Dispos"},{"key":"B32","doi-asserted-by":"publisher","first-page":"932934","DOI":"10.1155\/2015\/932934","article-title":"Comparison of different strategies for selection\/adaptation of mixed microbial cultures able to ferment crude glycerol derived from second-generation biodiesel","volume":"2015","author":"Varrone","year":"2015","journal-title":"Biomed. Res. Int"},{"key":"B33","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.metabol.2017.02.003","article-title":"Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism","volume":"70","author":"Wang","year":"","journal-title":"Metabolism"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.7150\/thno.18290","article-title":"Gut microbiota-mediated personalized treatment of hyperlipidemia using berberine","volume":"7","author":"Wang","year":"","journal-title":"Theranostics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1097\/00005344-199405000-00005","article-title":"Effects of berberine on delayed after depolarizations in ventricular muscles in vitro and in vivo","volume":"23","author":"Wang","year":"1994","journal-title":"J. Cardiovasc. Pharm"},{"key":"B36","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.apsb.2012.06.003","article-title":"Effects and mechanisms of berberine in diabetes treatment","volume":"2","author":"Yin","year":"2012","journal-title":"Acta. Pharm. Sin. B"},{"key":"B38","doi-asserted-by":"publisher","first-page":"36","DOI":"10.13699\/j.cnki.1001.6821.2000.01.010","article-title":"Determination and preliminary studies of metabolism of berberine in human urine after oral administration","volume":"16","author":"Yu","year":"2000","journal-title":"Chin. J. Clin. Pharmacol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.metabol.2009.07.029","article-title":"Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression","volume":"59","author":"Zhang","year":"2010","journal-title":"Metabolism"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e42529","DOI":"10.1371\/journal.pone.0042529","article-title":"Structural changes of gut microbiota during berberinemediated prevention of obesity and insulin resistance in high-fat diet-fed rats","volume":"7","author":"Zhang","year":"2012","journal-title":"PLoS ONE"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.1210\/jc.2007-2404","article-title":"Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine","volume":"93","author":"Zhang","year":"2008","journal-title":"J. Clin. Endocrinol. Metab"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1124\/dmd.106.011361","article-title":"Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography \/ ion trap mass spectrometry","volume":"34","author":"Zuo","year":"2006","journal-title":"Drug Metab. Dispos"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphar.2018.00214\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T04:30:14Z","timestamp":1521606614000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphar.2018.00214\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,21]]},"references-count":42,"alternative-id":["10.3389\/fphar.2018.00214"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2018.00214","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,21]]},"article-number":"214"}}