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Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites, and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME\/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.<\/jats:p>","DOI":"10.1021\/acs.jafc.7b02049","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T17:14:56Z","timestamp":1497546896000},"page":"5480-5493","source":"Crossref","is-referenced-by-count":110,"title":["Gastrointestinal Simulation Model TWIN-SHIME Shows\nDifferences between Human Urolithin-Metabotypes in Gut Microbiota\nComposition, Pomegranate Polyphenol Metabolism, and Transport along\nthe Intestinal Tract"],"prefix":"10.1021","volume":"65","author":[{"given":"Roci\u0301o","family":"Garci\u0301a-Villalba","sequence":"first","affiliation":[{"name":"CEBAS-CSIC , , ,","place":["Campus de Espinardo, Murcia, Spain, 30100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Vissenaekens","sequence":"additional","affiliation":[{"name":"Ghent University , , ,","place":["Ghent, Belgium"]},{"name":"Ghent University , , ,","place":["Kortrijk, Belgium"]},{"name":"Ghent University , , ,","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Pitart","sequence":"additional","affiliation":[{"name":"ProDigest BVBA , ,","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u0301a","family":"Romo-Vaquero","sequence":"additional","affiliation":[{"name":"CEBAS-CSIC , , ,","place":["Campus de Espinardo, Murcia, Spain, 30100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Espi\u0301n","sequence":"additional","affiliation":[{"name":"CEBAS-CSIC , , ,","place":["Campus de Espinardo, Murcia, Spain, 30100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Grootaert","sequence":"additional","affiliation":[{"name":"Ghent University , , ,","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u0301a V.","family":"Selma","sequence":"additional","affiliation":[{"name":"CEBAS-CSIC , , ,","place":["Campus de Espinardo, Murcia, Spain, 30100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katleen","family":"Raes","sequence":"additional","affiliation":[{"name":"Ghent University , , ,","place":["Kortrijk, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Smagghe","sequence":"additional","affiliation":[{"name":"Ghent University , , ,","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Possemiers","sequence":"additional","affiliation":[{"name":"ProDigest BVBA , ,","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Van Camp","sequence":"additional","affiliation":[{"name":"Ghent University , , ,","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0790-1739","authenticated-orcid":true,"given":"Francisco A.","family":"Tomas-Barberan","sequence":"additional","affiliation":[{"name":"CEBAS-CSIC , , ,","place":["Campus de Espinardo, Murcia, Spain, 30100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2017,6,15]]},"reference":[{"key":"2026090305251958200_cit1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.mam.2010.09.005","article-title":"Ellagitannins, Ellagic acid and Vascular\nHealth","volume":"31","author":"Larrosa","year":"2010","journal-title":"Mol. Aspects Med."},{"key":"2026090305251958200_cit2","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1080\/10408398.2011.644643","article-title":"Metabolic\nfate of ellagitannins: implications for health,\nand research perspectives for innovative functional foods","volume":"54","author":"Garci\u0301a-Mun\u0303oz","year":"2014","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"2026090305251958200_cit3","doi-asserted-by":"publisher","first-page":"6555","DOI":"10.1021\/acs.jafc.5b02062","article-title":"Validated\nmethod for the characterization\nand quantification of extractable and non-extractable ellagitannins\nafter acid hydrolysis in pomegranate fruits, juices and extracts","volume":"63","author":"Garci\u0301a-Villalba","year":"2015","journal-title":"J. Agric. 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Food Res."},{"key":"2026090305251958200_cit6","doi-asserted-by":"publisher","first-page":"6535","DOI":"10.1021\/jf5024615","article-title":"Ellagic acid metabolism by human\ngut microbiota: Consistent observation of three urolithin phenotypes\nin intervention trials, independent of food source, age, and health\nstatus","volume":"62","author":"Toma\u0301s-Barbera\u0301n","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"2026090305251958200_cit7","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1099\/ijs.0.055095-0","article-title":"Gordonibacter urolithinfaciens sp. nov., a urolithin-producing\nbacterium isolated from the human gut","volume":"64","author":"Selma","year":"2014","journal-title":"Int.\nJ. Syst. Evol. 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Immunol."},{"key":"2026090305251958200_cit42","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.phrs.2012.05.006","article-title":"Dietary\nsupplementation of an ellagic acid-enriched pomegranate extract attenuates\nchronic colonic inflammation in rats","volume":"66","author":"Rosillo","year":"2012","journal-title":"Pharmacol.\nRes."},{"key":"2026090305251958200_cit43","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1053\/gast.2001.27224","article-title":"Probiotic bacteria enhance murine and human intestinal\nepithelial barrier function","volume":"121","author":"Madsen","year":"2001","journal-title":"Gastroenterology"},{"key":"2026090305251958200_cit44","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s00394-003-0396-4","article-title":"Evaluation\nof the bioavailability and metabolism in the rat of punicalagin, an\nantioxidant polyphenol from pomegranate juice","volume":"42","author":"Cerda\u0301","year":"2003","journal-title":"Eur. J. 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