{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T23:14:02Z","timestamp":1763766842974,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>High fructose consumption is one of the hallmarks of Western diets and has been found to induce MeS symptoms in parallel to gut microbial dysbiosis. However, the causality between those two is still elusive. Here, we studied whether a significant modification of gut microbial composition by antibiotics can influence the fructose-induced metabolic changes. Male Sprague-Dawley (SD) rats were divided into four groups including controls, controls + antibiotics, high fructose diet (HFrD, 60% fructose), HFrD + antibiotics (n = 7\u20138 in each group) for a period of 8-weeks. The high fructose diet increased blood pressure (BP), triglyceride (TG), fatty liver and the expression of hepatic genes related to lipogenesis, and fructose transport and metabolism. In addition, fructose changed the microbial composition and increased acetic and butyric acids in fecal samples but not in the blood. Antibiotic treatment significantly reduced microbial diversity and modified the microbial composition in the samples. However, minimal or no effect was seen in the metabolic phenotypes. In conclusion, high fructose consumption (60%) induced metabolic changes and dysbiosis in rats. However, antibiotic treatment did not reverse the metabolic phenotype. Therefore, the metabolic changes are probably independent of a specific microbiome profile.<\/jats:p>","DOI":"10.3390\/nu12010203","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T03:20:22Z","timestamp":1579058422000},"page":"203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antibiotic Treatment Does Not Ameliorate the Metabolic Changes in Rats Presenting Dysbiosis After Consuming a High Fructose Diet"],"prefix":"10.3390","volume":"12","author":[{"given":"Ariel","family":"Bier","sequence":"first","affiliation":[{"name":"Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5265601, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rawan","family":"Khasbab","sequence":"additional","affiliation":[{"name":"Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5265601, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yael","family":"Haberman","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"},{"name":"The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan 5265601, Israel"},{"name":"Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzipi","family":"Braun","sequence":"additional","affiliation":[{"name":"The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan 5265601, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rotem","family":"Hadar","sequence":"additional","affiliation":[{"name":"The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan 5265601, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katya","family":"Sosnovski","sequence":"additional","affiliation":[{"name":"The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan 5265601, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amnon","family":"Amir","sequence":"additional","affiliation":[{"name":"The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan 5265601, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avshalom","family":"Leibowitz","sequence":"additional","affiliation":[{"name":"Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5265601, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehud","family":"Grossman","sequence":"additional","affiliation":[{"name":"Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5265601, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1007\/s11255-017-1544-8","article-title":"Dietary and commercialized fructose: Sweet or sour?","volume":"49","author":"Yerlikaya","year":"2017","journal-title":"Int. Urol. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1161\/CIR.0b013e31820a55f5","article-title":"Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association","volume":"123","author":"Heidenreich","year":"2011","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1161\/CIR.0000000000000485","article-title":"Heart Disease and Stroke Statistics\u20142017 Update: A Report From the American Heart Association","volume":"135","author":"Benjamin","year":"2017","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.gheart.2016.11.004","article-title":"20-Year Trend of CVD Risk Factors: Urban and Rural National Capital Region of India","volume":"12","author":"Prabhakaran","year":"2017","journal-title":"Glob. Heart"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E685","DOI":"10.1152\/ajpendo.00283.2010","article-title":"Fructose: A highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome","volume":"299","author":"Dekker","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1172\/JCI37385","article-title":"Consuming fructose-sweetened, not glucose-sweetened, beverages increase visceral adiposity and lipids and decrease insulin sensitivity in overweight\/obese men","volume":"1334","author":"Stanhope","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/MOL.0b013e3283613bca","article-title":"Adverse metabolic effects of dietary fructose: Results from the recent epidemiological, clinical, and mechanistic studies","volume":"24","author":"Stanhope","year":"2013","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1172\/JCI96702","article-title":"Fructose metabolism and metabolic disease","volume":"128","author":"Hannou","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41575-018-0061-2","article-title":"You are what you eat: Diet, health and the gut microbiota","volume":"16","author":"Zmora","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Do, M.H., Lee, E., Oh, M.J., Kim, Y., and Park, H.Y. (2018). High-Glucose or -Fructose Diet Cause Changes of the Gut Microbiota and Metabolic Disorders in Mice without Body Weight Change. Nutrients, 10.","DOI":"10.3390\/nu10060761"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jnutbio.2018.02.003","article-title":"Fructose liquid and solid formulations differently affect gut integrity, microbiota composition and related liver toxicity: A comparative in vivo study","volume":"55","author":"Mastrocola","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Di Luccia, B., Crescenzo, R., Mazzoli, A., Cigliano, L., Venditti, P., Walser, J.C., Widmer, A., Baccigalupi, L., Ricca, E., and Iossa, S. (2015). Rescue of fructose-induced metabolic syndrome by antibiotics or faecal transplantation in a rat model of obesity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134893"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.jnutbio.2015.05.011","article-title":"Diets rich in fructose, fat or fructose and fat alter intestinal barrier function and lead to the development of nonalcoholic fatty liver disease over time","volume":"26","author":"Sellmann","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"770","DOI":"10.3945\/jn.116.242859","article-title":"Intestinal Barrier Function and the Gut Microbiome Are Differentially Affected in Mice Fed a Western-Style Diet or Drinking Water Supplemented with Fructose","volume":"147","author":"Volynets","year":"2017","journal-title":"J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.jhep.2008.01.035","article-title":"Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin","volume":"48","author":"Bergheim","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1331657","DOI":"10.1080\/16546628.2017.1331657","article-title":"Dietary fructose causes defective insulin signalling and ceramide accumulation in the liver that can be reversed by gut microbiota modulation","volume":"61","author":"Crescenzo","year":"2017","journal-title":"Food Nutr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s40168-019-0713-7","article-title":"Dietary fructose-induced gut dysbiosis promotes mouse hippocampal neuroinflammation: A benefit of short-chain fatty acids","volume":"7","author":"Li","year":"2019","journal-title":"Microbiome"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"F423","DOI":"10.1152\/ajprenal.00124.2006","article-title":"Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats","volume":"292","author":"Tapia","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12986-016-0123-9","article-title":"Animal models of metabolic syndrome: A review","volume":"13","author":"Wong","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8364","DOI":"10.3748\/wjg.v20.i26.8364","article-title":"Experimental models of non-alcoholic fatty liver disease in rats","volume":"20","author":"Kucera","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.3945\/jn.109.105858","article-title":"Rats fed fructose-enriched diets have characteristics of nonalcoholic hepatic steatosis","volume":"139","author":"Kawasaki","year":"2009","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.2353\/ajpath.2006.050617","article-title":"Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents","volume":"168","author":"Ferrier","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.jhep.2011.01.048","article-title":"Lack of interleukin-1alpha or interleukin-1beta inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice","volume":"55","author":"Kamari","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41598-017-01217-1","article-title":"Fecal microbial characterization of hospitalized patients with suspected infectious diarrhea shows significant dysbiosis","volume":"7","author":"Braun","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/ismej.2012.8","article-title":"Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms","volume":"6","author":"Caporaso","year":"2012","journal-title":"ISME J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Flores, G.E., Henley, J.B., and Fierer, N. (2012). A direct PCR approach to accelerate analyses of human-associated microbial communities. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044563"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Amir, A., McDonald, D., Navas-Molina, J.A., Kopylova, E., Morton, J.T., Zech Xu, Z., Kightley, E.P., Thompson, L.R., Hyde, E.R., and Gonzalez, A. (2017). Deblur Rapidly Resolves Single-Nucleotide Community Sequence Patterns. mSystems, 2.","DOI":"10.1128\/mSystems.00191-16"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8228","DOI":"10.1128\/AEM.71.12.8228-8235.2005","article-title":"UniFrac: A new phylogenetic method for comparing microbial communities","volume":"71","author":"Lozupone","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_30","unstructured":"Mirarab, S., Nguyen, N., and Warnow, T. (2012). SEPP: SATe-enabled phylogenetic placement. Pac. Symp. Biocomput., 247\u2013258."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xu, Z.Z., Amir, A., Sanders, J., Zhu, Q., Morton, J.T., Bletz, M.C., Tripathi, A., Huang, S., McDonald, D., and Jiang, L. (2019). Calour: An Interactive, Microbe-Centric Analysis Tool. mSystems, 4.","DOI":"10.1128\/mSystems.00269-18"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1186\/gb-2012-13-9-r79","article-title":"Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment","volume":"13","author":"Morgan","year":"2012","journal-title":"Genome Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cho, Y.E., Kim, D.K., Seo, W., Gao, B., Yoo, S.H., and Song, B.J. (2019). Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress. Hepatology.","DOI":"10.1002\/hep.30652"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1172\/JCI81993","article-title":"ChREBP regulates fructose-induced glucose production independently of insulin signaling","volume":"126","author":"Kim","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kim, M., Astapova, I.I., Flier, S.N., Hannou, S.A., Doridot, L., Sargsyan, A., Kou, H.H., Fowler, A.J., Liang, G., and Herman, M.A. (2017). Intestinal, but not hepatic, ChREBP is required for fructose tolerance. JCI Insight, 2.","DOI":"10.1172\/jci.insight.96703"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Burgeiro, A., Cerqueira, M.G., Varela-Rodriguez, B.M., Nunes, S., Neto, P., Pereira, F.C., Reis, F., and Carvalho, E. (2017). Glucose and Lipid Dysmetabolism in a Rat Model of Prediabetes Induced by a High-Sucrose Diet. Nutrients, 9.","DOI":"10.20944\/preprints201704.0185.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12986-016-0074-1","article-title":"High-fructose and high-fat diet-induced disorders in rats: Impact on diabetes risk, hepatic and vascular complications","volume":"13","author":"Lozano","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1161\/01.HYP.0000182697.39687.34","article-title":"Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats","volume":"46","author":"Elmarakby","year":"2005","journal-title":"Hypertens (Dallas, Tex 1979)"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.cmet.2017.12.016","article-title":"The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids","volume":"27","author":"Jang","year":"2018","journal-title":"Cell Metab."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/203\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:19:37Z","timestamp":1760361577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,13]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["nu12010203"],"URL":"https:\/\/doi.org\/10.3390\/nu12010203","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2020,1,13]]}}}