{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:10:44Z","timestamp":1792465844575,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004374","name":"Chongqing Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>\n                    The increasing global incidence of precocious puberty, linked to environmental, metabolic, and genetic factors, necessitates innovative therapies beyond gonadotropin-releasing hormone (GnRH) analogs. Accumulating evidence implicates gut microbiota dysbiosis as a pivotal regulator of pubertal timing via interactions with hormone metabolism (e.g., estrogen reactivation via\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -glucuronidase), neuroendocrine pathways (nitric oxide signaling), and immune-inflammatory responses. This review delineates taxonomic alterations in central precocious puberty (CPP) and obesity-related subtypes, including\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    enrichment and\n                    <jats:italic>Alistipes<\/jats:italic>\n                    depletion, alongside functional shifts in microbial metabolite production. Mechanistic insights highlight microbiota-driven modulation of the hypothalamic\u2013pituitary-gonadal (HPG) axis, leptin\/insulin dynamics, and epigenetic regulation. Emerging interventions-probiotics, fecal microbiota transplantation (FMT), and dietary modifications-demonstrate efficacy in preclinical models and early clinical studies for delaying puberty onset and restoring hormonal balance. Translational efforts to validate these strategies are critical for addressing the clinical and psychosocial challenges posed by precocious puberty, positioning gut microbiota modulation as a novel therapeutic frontier in pediatric endocrinology.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2025.1596654","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T01:26:25Z","timestamp":1745544385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Research summary, possible mechanisms and perspectives of gut microbiota changes causing precocious puberty"],"prefix":"10.3389","volume":"12","author":[{"given":"Maorong","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3760\/cma.j.cn112140-20220802-00693","article-title":"Expert consensus on diagnosis and treatment of central precocious puberty","volume":"61","year":"2022","journal-title":"Chinese J Pediatrics"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.1007\/s00431-021-04022-1","article-title":"Diagnosis and management of precocious sexual maturation: an updated review","volume":"180","author":"Cheuiche","year":"2021","journal-title":"Eur J Pediatr"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S2213-8587(15)00380-0","article-title":"Causes, diagnosis, and treatment of central precocious puberty","volume":"4","author":"Latronico","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1038\/ijo.2012.177","article-title":"Pubertal timing and adult obesity and cardiometabolic risk in women and men: a systematic review and meta-analysis","volume":"37","author":"Prentice","year":"2013","journal-title":"Int J Obes"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"101262","DOI":"10.1016\/j.beem.2019.01.003","article-title":"Central precocious puberty, functional and tumor-related","volume":"33","author":"Soriano-Guill\u00e9n","year":"2019","journal-title":"Best Pract Res Cl En"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"4953","DOI":"10.1210\/jc.2009-1789","article-title":"Early age at menarche associated with cardiovascular disease and mortality","volume":"94","author":"Lakshman","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/cen.14475","article-title":"Central precocious puberty: recent advances in understanding the aetiology and in the clinical approach","volume":"95","author":"Maione","year":"2021","journal-title":"Clin Endocrinol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1107911","DOI":"10.3389\/fendo.2022.1107911","article-title":"Early and precocious puberty during the COVID-19 pandemic","volume":"13","author":"Prosperi","year":"2023","journal-title":"Front Endocrinol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"101579","DOI":"10.1016\/j.beem.2021.101579","article-title":"Endocrine-disrupting chemicals and their effects on puberty","volume":"35","author":"Lopez-Rodriguez","year":"2021","journal-title":"Best Pract Res Cl En"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.beem.2018.05.008","article-title":"Central precocious puberty: from genetics to treatment","volume":"32","author":"Aguirre","year":"2018","journal-title":"Best Pract Res Cl En"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/S0140-6736(03)12489-0","article-title":"Gut flora in health and disease","volume":"361","author":"Guarner","year":"2003","journal-title":"Lancet"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1159\/000518498","article-title":"Impact of delivery mode on infant gut microbiota","volume":"77","author":"Korpela","year":"2021","journal-title":"Ann Nutr Metab"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"343ra82","DOI":"10.1126\/scitranslmed.aad7121","article-title":"Antibiotics, birth mode, and diet shape microbiome maturation during early life","volume":"8","author":"Bokulich","year":"2016","journal-title":"Sci Transl Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1136\/gutjnl-2021-324767","article-title":"Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial","volume":"71","author":"Dierikx","year":"2022","journal-title":"Gut"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.fm.2017.09.001","article-title":"Human milk oligosaccharides and infant gut bifidobacteria: molecular strategies for their utilization","volume":"75","author":"Thomson","year":"2018","journal-title":"Food Microbiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e177","DOI":"10.1371\/journal.pbio.0050177","article-title":"Development of the human infant intestinal microbiota","volume":"5","author":"Palmer","year":"2007","journal-title":"PLoS Biol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nature11053","article-title":"Human gut microbiome viewed across age and geography","volume":"486","author":"Yatsunenko","year":"2012","journal-title":"Nature"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12934-020-01412-2","article-title":"Sexual dimorphism of gut microbiota at different pubertal status","volume":"19","author":"Yuan","year":"2020","journal-title":"Microb Cell Factories"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/s42003-024-06470-5","article-title":"The effect of testosterone on the gut microbiome in mice","volume":"7","author":"Moadi","year":"2024","journal-title":"Commun Biol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/s12967-023-04169-5","article-title":"Gut microbiome combined with metabolomics reveals biomarkers and pathways in central precocious puberty","volume":"21","author":"Huang","year":"2023","journal-title":"J Transl Med"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1438195","DOI":"10.3389\/fped.2024.1438195","article-title":"Causal relationship between the composition of the gut microbiota and central precocious puberty: a two-sample Mendelian randomization study","volume":"12","author":"Chen","year":"2024","journal-title":"Front Pediatr"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1186\/s12866-024-03461-8","article-title":"Alterations in the gut microbiota community are associated with childhood obesity and precocious puberty","volume":"24","author":"Wang","year":"2024","journal-title":"BMC Microbiol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"941","DOI":"10.3389\/fendo.2019.00941","article-title":"The Association of gut Microbiota with Idiopathic Central Precocious Puberty in girls","volume":"10","author":"Dong","year":"2020","journal-title":"Front Endocrinol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"109887","DOI":"10.1016\/j.isci.2024.109887","article-title":"Gut microbiota-metabolite interactions meditate the effect of dietary patterns on precocious puberty","volume":"27","author":"Wang","year":"2024","journal-title":"iScience"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.maturitas.2017.06.025","article-title":"Estrogen\u2013gut microbiome axis: physiological and clinical implications","volume":"103","author":"Baker","year":"2017","journal-title":"Maturitas"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.chom.2011.10.003","article-title":"Microbiome and malignancy","volume":"10","author":"Plottel","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/j.fertnstert.2015.10.021","article-title":"Introduction","volume":"104","author":"Franasiak","year":"2015","journal-title":"Fertil Steril"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1481364","DOI":"10.3389\/fendo.2024.1481364","article-title":"Metabolomic disorders caused by an imbalance in the gut microbiota are associated with central precocious puberty","volume":"15","author":"Liu","year":"2024","journal-title":"Front Endocrinol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41579-022-00805-x","article-title":"Bile acids and the gut microbiota: metabolic interactions and impacts on disease","volume":"21","author":"Collins","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/S0168-8278(99)80223-2","article-title":"Ursodeoxycholic acid prevents hepatic cytochrome P 450 isozyme reduction in rats with deoxycholic acid-induced liver injury","volume":"31","author":"Tanaka","year":"1999","journal-title":"J Hepatol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"109249","DOI":"10.1016\/j.steroids.2023.109249","article-title":"Structures and functions of human placental aromatase and steroid sulfatase, two key enzymes in estrogen biosynthesis","volume":"196","author":"Ghosh","year":"2023","journal-title":"Steroids"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1449033","DOI":"10.3389\/fendo.2024.1449033","article-title":"Interaction between vitamin D homeostasis, gut microbiota, and central precocious puberty","volume":"15","author":"Guo","year":"2024","journal-title":"Front Endocrinol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e299","DOI":"10.1002\/ctm2.299","article-title":"Altered nitric oxide induced by gut microbiota reveals the connection between central precocious puberty and obesity","volume":"11","author":"Li","year":"2021","journal-title":"Clin Transl Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fendo.2022.1051797","article-title":"Gut microbiota and its derived SCFAs regulate the HPGA to reverse obesity-induced precocious puberty in female rats","volume":"13","author":"Wang","year":"2022","journal-title":"Front Endocrinol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1097\/MOP.0000000000001035","article-title":"The link between obesity and puberty: what is new?","volume":"33","author":"Huang","year":"2021","journal-title":"Curr Opin Pediatr"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e40962","DOI":"10.1016\/j.heliyon.2024.e40962","article-title":"Inflammation and oxidative stress processes in induced precocious puberty in rats","volume":"10","author":"Pop","year":"2024","journal-title":"Heliyon"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"913334","DOI":"10.3389\/fendo.2022.913334","article-title":"Current evidence on the impact of the COVID-19 pandemic on paediatric endocrine conditions","volume":"13","author":"Gnocchi","year":"2022","journal-title":"Front Endocrinol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"119","DOI":"10.5051\/jpis.2010.40.3.119","article-title":"Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-\u03b1 in monocyte-derived macrophages","volume":"40","author":"Kim","year":"2010","journal-title":"J Periodontal Implant Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1, 5","DOI":"10.3928\/19382359-20230102-06","article-title":"Metabolic consequences of pediatric obesity: a review of pathophysiology, screening, and treatment","volume":"52","author":"Gunaratne","year":"2023","journal-title":"Pediatr Ann"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"985","DOI":"10.3390\/antiox13080985","article-title":"Gut microbiota Dysbiosis, oxidative stress, inflammation, and epigenetic alterations in metabolic diseases","volume":"13","author":"Mostafavi Abdolmaleky","year":"2024","journal-title":"Antioxidants"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3390\/children10020241","article-title":"Links between childhood obesity, high-fat diet, and central precocious puberty","volume":"10","author":"Calcaterra","year":"2023","journal-title":"Child Aust"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1412640","DOI":"10.3389\/fimmu.2024.1412640","article-title":"Global research progress of gut microbiota and epigenetics: bibliometrics and visualized analysis","volume":"15","author":"Tian","year":"2024","journal-title":"Front Immunol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2200501","DOI":"10.1002\/mnfr.202200501","article-title":"Intervention effect of probiotics on the early onset of puberty induced by Daidzein in female mice","volume":"67","author":"Yuan","year":"2023","journal-title":"Mol Nutr Food Res"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1002\/dev.21765","article-title":"Early-life stress leads to sex-dependent changes in pubertal timing in rats that are reversed by a probiotic formulation","volume":"61","author":"Cowan","year":"2019","journal-title":"Dev Psychobiol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"854477","DOI":"10.3389\/fpubh.2022.854477","article-title":"Association of the consumption of common drinks with early puberty in both sexes","volume":"10","author":"Tsai","year":"2022","journal-title":"Front Public Health"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"930747","DOI":"10.3389\/fmicb.2022.930747","article-title":"Effects of high-fat diet during childhood on precocious puberty and gut microbiota in mice","volume":"13","author":"Bo","year":"2022","journal-title":"Front Microbiol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"122789","DOI":"10.1016\/j.lfs.2024.122789","article-title":"Natural sweetener glycyrrhizin protects against precocious puberty by modulating the gut microbiome","volume":"350","author":"Nguyen","year":"2024","journal-title":"Life Sci"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqz041","article-title":"Microbial reconstitution reverses early female puberty induced by maternal high-fat diet during lactation","volume":"161","author":"Wang","year":"2020","journal-title":"Endocrinology"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1111\/ijfs.13410","article-title":"Escherichia coli biotransformation of daidzein fermentation products from soy-based foods\u2014relevance to food oestrogenicity-based functionality","volume":"52","author":"Ye","year":"2017","journal-title":"Int J Food Sci Technol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.3390\/children10101686","article-title":"Breast and formula Milk and early puberty onset","volume":"10","author":"Calcaterra","year":"2023","journal-title":"Child Aust"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/7175250","article-title":"Distinct gut microbiota structure and function of children with idiopathic central and peripheral precocious puberty","volume":"2022","author":"Huang","year":"2022","journal-title":"Int J Endocrinol"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"11169","DOI":"10.1039\/D4FO03844D","article-title":"Mechanistic insights into EGCG\u2019s preventive effects on obesity-induced precocious puberty through multi-omics analyses","volume":"15","author":"Gu","year":"2024","journal-title":"Food Funct"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1596654\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T01:26:27Z","timestamp":1745544387000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1596654\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":52,"alternative-id":["10.3389\/fnut.2025.1596654"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1596654","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,25]]},"article-number":"1596654"}}