{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:01:05Z","timestamp":1792404065282,"version":"4.4.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>\n                    Sucralose is a non-nutritive artificial sweetener (NNS) used in foods or beverages to control blood glucose levels and body weight gain. The consumption of NNS has increased in recent years over the world, and many researches have indicated long-term sucralose administration altered the gut microbiome composition of mice. These studies all focus on the US Food and Drug Administration (FDA) defined acceptable daily intake (ADI), approximately 5 mg\/kg BW\/day for human. In our study, mice were given with T1-4 (0.0003, 0.003, 0.03, and 0.3 mg\/mL) of sucralose, respectively, Control group mice were given normal water. In particular, 0.3 mg\/mL of sucralose was equal to the ADI (5 mg\/kg BW\/day). After 16 weeks, all mice were weighted and sacrificed, the liver of each mouse was isolated and weighed, segments of jejunum, ileum and colon were collected for H&amp;amp;E-stained. The contents of jejunum, ileum, cecum and colon were collected for 16S rRNA gene sequencing. The results showed sucralose administration affects the intestinal barrier function evidenced by distinct lymphocyte aggregation in ileum and colon while not change the mice body weight. The 16S rRNA gene sequencing of the mice gut microbiome suggested sucralose administration significantly changed the composition of gut microbiota, especially in T1 and T4 group. For example, a reduction of probiotics abundance (\n                    <jats:italic>Lachnoclostridium<\/jats:italic>\n                    and\n                    <jats:italic>Lachnospiraceae<\/jats:italic>\n                    ) was found in cecum of T4 group mice compared with Control group. On the other hand,\n                    <jats:italic>Allobaculum<\/jats:italic>\n                    , which was reported positively correlated with diabetes, was increased in the T1 and T4 group. In addition, the potential pathogens, including\n                    <jats:italic>Tenacibaculum, Ruegeria, Staphylococcus<\/jats:italic>\n                    were also increased in jejunum, ileum and colon by sucralose administration in T1 and T4 group. These new findings indicate that low dose of sucralose (T1) alter gut microbiome in mice, and these adverse health effects are equal to ADI level (T4). Overall, our study provides guidance and suggestions for the use of sucralose in foods and beverages.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2022.848392","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T04:29:48Z","timestamp":1645763388000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Low Dose of Sucralose Alter Gut Microbiome in Mice"],"prefix":"10.3389","volume":"9","author":[{"given":"Zibin","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingping","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.fct.2017.06.046","article-title":"Sweeteners as food additives in the XXI century: a review of what is known, and what is to come","volume":"107","author":"Carocho","year":"2017","journal-title":"Food Chem Toxicol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1093\/nutrit\/nuw032","article-title":"Biological fate of low-calorie sweeteners","volume":"74","author":"Magnuson","year":"2016","journal-title":"Nutr Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/B978-0-12-407691-4.00010-1","article-title":"Sucralose","volume":"38","author":"AlDeeb","year":"2013","journal-title":"Profiles Drug Subst Excip Relat Methodol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"357","DOI":"10.3390\/nu10030357","article-title":"Low-\/no-calorie sweeteners: a review of global intakes","volume":"10","author":"Martyn","year":"2018","journal-title":"Nutrients."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1080\/19490976.2020.1738187","article-title":"Maternal sucralose intake alters gut microbiota of offspring and exacerbates hepatic steatosis in adulthood","volume":"11","author":"Dai","year":"2020","journal-title":"Gut Microbes."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.3389\/fmicb.2019.01360","article-title":"Maternal exposure to non-nutritive sweeteners impacts progeny's metabolism and microbiome","volume":"10","author":"Olivier-Van Stichelen","year":"2019","journal-title":"Front Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1016\/S0278-6915(00)00026-0","article-title":"Sucralose metabolism and pharmacokinetics in man","volume":"38","author":"Roberts","year":"2000","journal-title":"Food Chem Toxicol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3945\/ajcn.112.034751","article-title":"Low-calorie sweetener consumption is increasing in the United States","volume":"96","author":"Sylvetsky","year":"2012","journal-title":"Am J Clin Nutr."},{"key":"B9","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3390\/nu9060560","article-title":"Effects of low-dose non-caloric sweetener consumption on gut microbiota in mice","volume":"9","author":"Uebanso","year":"2017","journal-title":"Nutrients."},{"key":"B10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1146\/annurev.mi.31.100177.000543","article-title":"Microbial ecology of the gastrointestinal tract","volume":"31","author":"Savage","year":"1977","journal-title":"Annu Rev Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1007\/s10482-020-01474-7","article-title":"Human gut microbiota\/microbiome in health and diseases: a review","volume":"113","author":"Gomaa","year":"2020","journal-title":"Antonie Van Leeuwenhoek."},{"key":"B12","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1136\/gutjnl-2020-321747","article-title":"Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health","volume":"70","author":"Fassarella","year":"2021","journal-title":"Gut."},{"key":"B13","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat Rev Microbiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1080\/15287390802328630","article-title":"Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats","volume":"71","author":"Abou-Donia","year":"2008","journal-title":"J Toxicol Environ Health A."},{"key":"B15","doi-asserted-by":"publisher","first-page":"756","DOI":"10.3390\/nu9070756","article-title":"Effects of consuming xylitol on gut microbiota and lipid metabolism in mice","volume":"9","author":"Uebanso","year":"2017","journal-title":"Nutrients."},{"key":"B16","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1017\/S0007114519001570","article-title":"Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults","volume":"122","author":"Thomson","year":"2019","journal-title":"Br J Nutr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.3390\/nu12113408","article-title":"The effects of non-nutritive artificial sweeteners, aspartame and sucralose, on the gut microbiome in healthy adults: secondary outcomes of a randomized double-blinded crossover clinical trial","volume":"12","author":"Ahmad","year":"2020","journal-title":"Nutrients."},{"key":"B18","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nature13793","article-title":"Artificial sweeteners induce glucose intolerance by altering the gut microbiota","volume":"514","author":"Suez","year":"2014","journal-title":"Nature."},{"key":"B19","doi-asserted-by":"publisher","first-page":"690138","DOI":"10.3389\/fnut.2021.690138","article-title":"Allobaculum Involves in the modulation of intestinal ANGPTLT4 expression in mice treated by high-fat diet","volume":"8","author":"Zheng","year":"2021","journal-title":"Front Nutr."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3045","DOI":"10.3389\/fmicb.2018.03045","article-title":"Gut microbiota is a major contributor to adiposity in pigs","volume":"9","author":"Yang","year":"2018","journal-title":"Front Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1021\/acs.jafc.0c07095","article-title":"Preventive and therapeutic spermidine treatment attenuates acute colitis in mice","volume":"69","author":"Ma","year":"2021","journal-title":"J Agric Food Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s40104-017-0170-8","article-title":"Association of growth rate with hormone levels and myogenic gene expression profile in broilers","volume":"8","author":"Xiao","year":"2017","journal-title":"J Anim Sci Biotechnol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1080\/19490976.2020.1773748","article-title":"Life-long dynamics of the swine gut microbiome and their implications in probiotics development and food safety","volume":"11","author":"Li","year":"2020","journal-title":"Gut Microbes."},{"key":"B24","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.neubiorev.2019.05.021","article-title":"The impact of sugar consumption on stress driven, emotional and addictive behaviors","volume":"103","author":"Jacques","year":"2019","journal-title":"Neurosci Biobehav Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1039\/D0FO02424D","article-title":"A rational review on the effects of sweeteners and sweetness enhancers on appetite, food reward and metabolic\/adiposity outcomes in adults","volume":"12","author":"O'Connor","year":"2021","journal-title":"Food Funct."},{"key":"B27","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/10937404.2013.842523","article-title":"Sucralose, a synthetic organochlorine sweetener: overview of biological issues","volume":"16","author":"Schiffman","year":"2013","journal-title":"J Toxicol Environ Health B Crit Rev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/j.eprac.2021.06.013","article-title":"Artificial sweeteners for obesity-better than sugary alternatives potentially a solution","volume":"27","author":"Nadolsky","year":"2021","journal-title":"Endocr Pract."},{"key":"B29","doi-asserted-by":"publisher","first-page":"E929","DOI":"10.1503\/cmaj.161390","article-title":"Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies","volume":"189","author":"Azad","year":"2017","journal-title":"Cmaj."},{"key":"B30","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1053\/j.gastro.2016.07.008","article-title":"Inflammation and the intestinal barrier: leukocyte-epithelial cell interactions, cell junction remodeling, and mucosal repair","volume":"151","author":"Luissint","year":"2016","journal-title":"Gastroenterology."},{"key":"B31","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nri3738","article-title":"Regional specialization within the intestinal immune system","volume":"14","author":"Mowat","year":"2014","journal-title":"Nat Rev Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1053\/j.gastro.2020.04.077","article-title":"Contribution of the intestinal microbiome and gut barrier to hepatic disorders","volume":"159","author":"Chopyk","year":"2020","journal-title":"Gastroenterology."},{"key":"B33","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: a therapeutic target?","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1053\/j.gastro.2020.03.007","article-title":"Serum biomarkers identify patients who will develop inflammatory bowel diseases up to 5 years before diagnosis","volume":"159","author":"Torres","year":"2020","journal-title":"Gastroenterology."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.2337\/dc12-9002","article-title":"Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the american heart association and the american diabetes association","volume":"35","author":"Gardner","year":"2012","journal-title":"Diabetes Care."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.3390\/nu12061862","article-title":"Artificial sweeteners disrupt tight junctions and barrier function in the intestinal epithelium through activation of the sweet taste receptor, T1R3","volume":"12","author":"Shil","year":"2020","journal-title":"Nutrients."},{"key":"B37","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3389\/fphys.2017.00487","article-title":"Gut microbiome response to sucralose and its potential role in inducing liver inflammation in mice","volume":"8","author":"Bian","year":"2017","journal-title":"Front Physiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"6402","DOI":"10.3390\/ijms21176402","article-title":"Gut microbiota and intestinal trans-epithelial permeability","volume":"21","author":"Allam-Ndoul","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cmet.2020.11.010","article-title":"Current concepts, opportunities, and challenges of gut microbiome-based personalized medicine in nonalcoholic fatty liver disease","volume":"33","author":"Sharpton","year":"2021","journal-title":"Cell Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"119622","DOI":"10.1016\/j.lfs.2021.119622","article-title":"Restoration of dysbiotic human gut microbiome for homeostasis","volume":"278","author":"Dixit","year":"2021","journal-title":"Life Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1801301","DOI":"10.1080\/19490976.2020.1801301","article-title":"The development of metabolic endotoxemia is dependent on the type of sweetener and the presence of saturated fat in the diet","volume":"12","author":"S\u00e1nchez-Tapia","year":"2020","journal-title":"Gut Microbes."},{"key":"B42","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1093\/advances\/nmy037","article-title":"Effects of sweeteners on the gut microbiota: a review of experimental studies and clinical trials","volume":"10","author":"Ruiz-Ojeda","year":"2019","journal-title":"Adv Nutr."},{"key":"B43","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s40168-019-0721-7","article-title":"Longitudinal investigation of the swine gut microbiome from birth to market reveals stage and growth performance associated bacteria","volume":"7","author":"Wang","year":"2019","journal-title":"Microbiome."},{"key":"B44","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/nature11237","article-title":"Defining the core Arabidopsis thaliana root microbiome","volume":"488","author":"Lundberg","year":"2012","journal-title":"Nature."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1101\/gr.085464.108","article-title":"Microbial community profiling for human microbiome projects: tools, techniques, and challenges","volume":"19","author":"Hamady","year":"2009","journal-title":"Genome Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e0199080","DOI":"10.1371\/journal.pone.0199080","article-title":"Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice","volume":"13","author":"Wang","year":"2018","journal-title":"PLoS ONE."},{"key":"B47","doi-asserted-by":"publisher","first-page":"7046","DOI":"10.1038\/s41598-017-07335-0","article-title":"Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through promoting the growth of gut butyrate-producing bacteria in type 2 diabetic mice","volume":"7","author":"Jia","year":"2017","journal-title":"Sci Rep."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e13991","DOI":"10.1111\/jfbc.13991","article-title":"Effects of L-arabinose by hypoglycemic and modulating gut microbiome in a high-fat diet- and streptozotocin-induced mouse model of type 2 diabetes mellitus","volume":"45","author":"Shen","year":"2021","journal-title":"J Food Biochem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.3390\/pathogens9121029","article-title":"Advancements in characterizing tenacibaculum infections in Canada","volume":"9","author":"Nowlan","year":"2020","journal-title":"Pathogens."},{"key":"B50","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00338-021-02075-0","article-title":"Shifts in marine invertebrate bacterial assemblages associated with tissue necrosis during a heatwave","volume":"40","author":"Rubio-Portillo","year":"2021","journal-title":"Coral Reefs."},{"key":"B51","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.mib.2020.02.005","article-title":"Staphylococcus aureus bloodstream infections: pathogenesis and regulatory mechanisms","volume":"53","author":"Kwiecinski","year":"2020","journal-title":"Curr Opin Microbiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/s41366-019-0332-1","article-title":"Resveratrol-induced gut microbiota reduces obesity in high-fat diet-fed mice","volume":"44","author":"Wang","year":"2020","journal-title":"Int J Obes (Lond)."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.4014\/jmb.2002.02044","article-title":"Fecal microbiota transplantation (FMT) alleviates experimental colitis in mice by gut microbiota regulation","volume":"30","author":"Zhang","year":"2020","journal-title":"J Microbiol Biotechnol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2020.1832857","article-title":"Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice","volume":"12","author":"Ma","year":"2020","journal-title":"Gut Microbes."},{"key":"B55","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/microorganisms8040573","article-title":"The controversial role of human gut lachnospiraceae","volume":"8","author":"Vacca","year":"2020","journal-title":"Microorganisms."},{"key":"B56","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.cell.2014.05.052","article-title":"Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences","volume":"158","author":"Cox","year":"2014","journal-title":"Cell."},{"key":"B57","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41586-020-2634-9","article-title":"Gut microorganisms act together to exacerbate inflammation in spinal cords","volume":"585","author":"Miyauchi","year":"2020","journal-title":"Nature."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1966278","DOI":"10.1080\/19490976.2021.1966278","article-title":"Identification of Allobaculum mucolyticum as a novel human intestinal mucin degrader","volume":"13","author":"van Muijlwijk","year":"2021","journal-title":"Gut Microbes."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.848392\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T04:29:50Z","timestamp":1645763390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.848392\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":58,"alternative-id":["10.3389\/fnut.2022.848392"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.848392","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]},"article-number":"848392"}}