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The study investigates the effects of the long\u2010term intake of aspartame on puberty and GM in animals and humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Aspartame\u2010fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>aspartame treatment decreases the mRNA levels of gonadotropin\u2010releasing hormone (GnRH), Kiss1, and G protein\u2010coupled receptor 54 (GPR54), increases the mRNA level of RFamide\u2010related peptide\u20103 (RFRP\u20103), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>aspartame treatment. Among which,<jats:italic>Escherichia\u2013Shigella<\/jats:italic>is negatively correlated with several SCFAs. In girls, high\u2010dose aspartame consumption decreases the risk of precocious puberty.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>aspartame\u2010fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1\/GPR54 system and inducing the RFRP\u20103. An acceptable dose of aspartame should be recommended during childhood.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300270","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T05:25:02Z","timestamp":1708665902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Aspartame Intake Delayed Puberty Onset in Female Offspring Rats and Girls"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8864-2777","authenticated-orcid":false,"given":"Chia\u2010Yuan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Food Science National Taiwan Ocean University Keelung 202301 Taiwan"},{"name":"Department of Family Medicine School of Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam Nhat","family":"Nguyen","sequence":"additional","affiliation":[{"name":"College of Medicine Taipei Medical University Taipei 110 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Ling","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Family Medicine School of Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan"},{"name":"Department of Health Promotion and Gerontological Care College of LOHAS Taipei University of Marine Technology New Taipei City 25172 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010Hong","family":"Hsieh","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences College of Nutrition Taipei Medical University Taipei 110 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Tsung","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine College of Medicine National Cheng Kung University Tainan 701 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-3716","authenticated-orcid":false,"given":"Yang\u2010Ching","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Family Medicine School of Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan"},{"name":"School of Nutrition and Health Sciences College of Nutrition Taipei Medical University Taipei 110 Taiwan"},{"name":"Department of Family Medicine Taipei Medical University Hospital Taipei 11031 Taiwan"},{"name":"Graduate Institute of Metabolism and Obesity Sciences Taipei Medical University Taipei 110 Taiwan"},{"name":"Department of Family Medicine Wan Fang Hospital, Taipei Medical University Taipei 116 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00418-0"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2020.08.002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-815590"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2018.05.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-15-0113"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins7114668"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327110364638"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112740"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.100958"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nux035"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejcn.1602866"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2019.04.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijir.2017.17"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqz041"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13793"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R036012"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00941"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsams.2006.05.003"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S136898002200088X"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00380-0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/1978043","volume":"2020","author":"Hu K.","year":"2020","journal-title":"Evid. 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