{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:39:24Z","timestamp":1790123964410,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,5]],"date-time":"2019-01-05T00:00:00Z","timestamp":1546646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R00AA023266"],"award-info":[{"award-number":["R00AA023266"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Gut dysbiosis and altered short-chain fatty acids are associated with ethanol-induced liver injury. SCFA are fermentation byproducts of the gut microbiota known to have many beneficial biological effects. We tested if a designer synbiotic could protect against ethanol-induced gut-liver injury. C57BL\/6 female mice were exposed to chronic-binge ethanol feeding consisting of ethanol (5% vol\/vol) for 10 days, followed by a single gavage (5 g\/kg body weight) 6 h before euthanasia. A group of mice also received oral supplementation daily with a designer synbiotic, and another group received fecal slurry (FS); control animals received saline. Control mice were isocalorically substituted maltose dextran for ethanol over the entire exposure period. Ethanol exposure reduced expression of tight junction proteins in the proximal colon and induced hepatocyte injury and steatosis. Synbiotic supplementation not only mitigated losses in tight junction protein expression, but also prevented ethanol-induced steatosis and hepatocyte injury. Ethanol exposure also increased hepatic inflammation and oxidative stress, which was also attenuated by synbiotic supplementation. Mice receiving FS were not protected from ethanol-induced liver injury or steatosis. Results were associated with luminal SCFA levels and SCFA transporter expression in the proximal colon and liver. These results indicate supplementation with a designer synbiotic is effective in attenuating chronic-binge ethanol-induced gut-liver injury and steatosis in mice, and highlight the beneficial effects of the gut microbial fermentation byproducts.<\/jats:p>","DOI":"10.3390\/nu11010097","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T03:06:06Z","timestamp":1547003166000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["A Designer Synbiotic Attenuates Chronic-Binge Ethanol-Induced Gut-Liver Injury in Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Sanjoy","family":"Roychowdhury","sequence":"first","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Glueck","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Ali","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Nutrition Research Center, U.S. Department of Agriculture\/Agricultural Research Service, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-7099","authenticated-orcid":false,"given":"Gail A. M.","family":"Cresci","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Department of Pediatric Gastroenterology, Cleveland Clinic Children\u2019s Hospital, Cleveland, OH 44195, USA"},{"name":"Center for Human Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jhep.2017.11.006","article-title":"The bidirectional impacts of alcohol consumption and the metabolic syndrome: Cofactors for progressive fatty liver disease","volume":"68","author":"Boyle","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1172\/JCI116334","article-title":"Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver","volume":"91","author":"Oshita","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Osna, N.A., and Kharbanda, K.K. (2016). Multi-organ alcohol-related damage: Mechanisms and treatment. Biomolecules, 6.","DOI":"10.3390\/biom6020020"},{"key":"ref_4","first-page":"245","article-title":"Overview: How Is Alcohol Metabolized by the Body?","volume":"29","author":"Zakhari","year":"2006","journal-title":"Annu. Rev. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Li, F., Duan, K., Wang, C., Mcclain, C., and Feng, W. (2015). Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms. Gastroenterol. Res. Pract., 2016.","DOI":"10.1155\/2016\/5491465"},{"key":"ref_6","first-page":"223","article-title":"The Gastrointestinal Microbiome","volume":"37","author":"Engen","year":"2015","journal-title":"Alcohol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1021\/pr400362z","article-title":"Chronic ethanol consumption alters mammalian gastrointestinal content metabolites","volume":"12","author":"Xie","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S1499-3872(14)60044-8","article-title":"Sodium butyrate protects against toxin-induced acute liver failure in rats","volume":"13","author":"Yang","year":"2014","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21069","DOI":"10.3390\/ijms151121069","article-title":"Inhibition of histone deacetylase by butyrate protects rat liver from ischemic reperfusion injury","volume":"15","author":"Sun","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cresci, G.A., Glueck, B., McMullen, M.R., Xin, W., Allende, D., and Nagy, L.E. (2017). Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury. J. Gastroenterol. Hepatol., 32.","DOI":"10.1111\/jgh.13731"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cresci, G.A., Bush, K., and Nagy, L.E. (2014). Tributyrin supplementation protects mice from acute ethanol-induced gut injury. Alcohol. Clin. Exp. Res., 38.","DOI":"10.1111\/acer.12428"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document: The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.alcohol.2008.08.006","article-title":"Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: A pilot study","volume":"42","author":"Kirpich","year":"2008","journal-title":"Alcohol"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Barone, R., Rappa, F., Macaluso, F., Bavisotto, C.C., Sangiorgi, C., Di Paola, G., Tomasello, G., Di Felice, V., Marcian\u00f2, V., and Farina, F. (2016). Alcoholic liver disease: A mouse model reveals protection by Lactobacillus fermentum. Clin. Transl. Gastroenterol., 7.","DOI":"10.1038\/ctg.2015.66"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-11734-8","article-title":"Butyrate-producing bacteria supplemented in vitro to Crohn\u2019s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity","volume":"7","author":"Geirnaert","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s10787-018-0479-8","article-title":"Probiotic mixture of Lactobacillus and Bifidobacterium alleviates systemic adiposity and inflammation in non-alcoholic fatty liver disease rats through Gpr109a and the commensal metabolite butyrate","volume":"26","author":"Liang","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Carlson, J.L., Erickson, J.M., Lloyd, B.B., and Slavin, J.L. (2018). Health Effects and Sources of Prebiotic Dietary Fiber. Curr. Dev. Nutr., 1\u20138.","DOI":"10.1093\/cdn\/nzy005"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1002\/jpen.1053","article-title":"Faecalibacterium prausnitzii and a Prebiotic Protect Intestinal Health in a Mouse Model of Antibiotic and Clostridium difficile Exposure","volume":"42","author":"Roychowdhury","year":"2018","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E700","DOI":"10.1152\/ajpendo.00052.2013","article-title":"Regulation of lipid synthesis genes and milk fat production in human mammary epithelial cells during secretory activation","volume":"305","author":"Mohammad","year":"2013","journal-title":"AJP Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/advances\/nmx009","article-title":"Butyrate: A double-edged sword for health?","volume":"9","author":"Liu","year":"2018","journal-title":"Adv. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.pbj.2016.04.004","article-title":"Regulation of colonic epithelial butyrate transport: Focus on colorectal cancer","volume":"1","author":"Martel","year":"2016","journal-title":"Porto Biomed. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kritchevsky, D., and Bonfield, C. (1997). Butyrate and the colonocyte: production, absorption, metabolism, and therapeutic implications. Dietary Fiber in Health and Disease, Plenum Press.","DOI":"10.1007\/978-1-4615-5967-2"},{"key":"ref_23","unstructured":"Mitic, L.L., and Anderson, J.M. (1971). Molecular architecture. Nat. New Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/nure.12027","article-title":"Ethanol metabolism and its effects on the intestinal epithelial barrier","volume":"71","author":"Elamin","year":"2013","journal-title":"Nutr. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e996","DOI":"10.1038\/cddis.2013.499","article-title":"Molecular mechanisms of hepatic apoptosis","volume":"5","author":"Wang","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.fusengdes.2017.04.086","article-title":"Visible imaging measurement of position and displacement of the last closed flux surface in EAST tokamak","volume":"119","author":"Wang","year":"2017","journal-title":"Fusion Eng. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1007\/s00394-017-1568-y","article-title":"Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: A systematic review and meta-analysis","volume":"57","author":"Khalesi","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/ajcn\/73.2.415s","article-title":"Prebiotic digestion and fermentation","volume":"73","author":"Cummings","year":"2001","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1194\/jlr.R067629","article-title":"Short- and medium-chain fatty acids in energy metabolism: The cellular perspective","volume":"57","author":"Wojtczak","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_30","first-page":"1","article-title":"Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis","volume":"362","author":"Gueimonde","year":"2015","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1017\/S0007114500002038","article-title":"Potato and high-amylose maize starches are not equivalent producers of butyrate for the colonic mucosa","volume":"84","author":"Martin","year":"2000","journal-title":"Br. J. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nrgastro.2012.156","article-title":"The role of the gut microbiota in nutrition and health","volume":"9","author":"Flint","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1365-2036.2007.03562.x","article-title":"Review article: The role of butyrate on colonic function","volume":"27","author":"Hamer","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.00300-15","article-title":"Identification of Metabolic Signatures Linked to Anti-Inflammatory Effects of Faecalibacterium prausnitzii","volume":"6","author":"Miquel","year":"2015","journal-title":"MBio"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/ismej.2017.24","article-title":"Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice","volume":"11","author":"Munukka","year":"2017","journal-title":"ISME J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/1462-2920.13589","article-title":"Formation of propionate and butyrate by the human colonic microbiota","volume":"19","author":"Louis","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref_37","first-page":"3593","article-title":"Two Routes of Metabolic Cross-Feeding between","volume":"72","author":"Belenguer","year":"2006","journal-title":"Society"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"G900","DOI":"10.1152\/ajpgi.00265.2013","article-title":"Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids","volume":"305","author":"Lange","year":"2013","journal-title":"AJP Gastrointest. Liver Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1079\/BJN20041150","article-title":"Contribution of acetate to butyrate formation by human faecal bacteria","volume":"91","author":"Duncan","year":"2004","journal-title":"Br. J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/bies.201300073","article-title":"Intestinal colonization: How key microbial players become established in this dynamic process: Microbial metabolic activities and the interplay between the host and microbes Prospects & Overviews S. E. Aidy et al.","volume":"35","author":"Louis","year":"2013","journal-title":"BioEssays"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Cresci, G.A., Thangaraju, M., Mellinger, J.D., Liu, K., and Ganapathy, V. (2010). Colonic gene expression in conventional and germ-free mice with a focus on the butyrate receptor GPR109A and the butyrate transporter SLC5A8. J. Gastrointest. Surg., 14.","DOI":"10.1007\/s11605-009-1045-x"},{"key":"ref_42","first-page":"299","article-title":"Short-chain fatty acid transporters: role in colonic homeostasis","volume":"8","author":"Sivaprakasam","year":"2018","journal-title":"Compr Physiol"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cbpb.2005.03.003","article-title":"Expression of MCT1, MCT2 and MCT4 in the rumen, small intestine and liver of reindeer (Rangifer tarandus tarandus L.)","volume":"141","author":"Koho","year":"2005","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00232-011-9340-3","article-title":"Characterization of butyrate uptake by nontransformed intestinal epithelial cell lines","volume":"240","author":"Goncalves","year":"2011","journal-title":"J. Membr. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ejphar.2012.11.029","article-title":"The effect of oxidative stress upon the intestinal epithelial uptake of butyrate","volume":"699","author":"Catarino","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1002\/mnfr.201600305","article-title":"Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity","volume":"60","author":"Weitkunat","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2337\/db16-0924","article-title":"Butyrate regulates liver mitochondrial function, efficiency, and dynamics in insulin-resistant obese mice","volume":"66","author":"Mollica","year":"2017","journal-title":"Diabetes"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/1\/97\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:23:43Z","timestamp":1760185423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/1\/97"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,5]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["nu11010097"],"URL":"https:\/\/doi.org\/10.3390\/nu11010097","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,5]]}}}