{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:53:09Z","timestamp":1793832789434,"version":"4.6.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Catch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of <jats:italic>Lactobacillus<\/jats:italic> in the CUG-SGA group. The decrease in <jats:italic>Lactobacillus<\/jats:italic> was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in <jats:italic>Lactobacillus<\/jats:italic> bacteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Lactobacillus<\/jats:italic> and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.630526","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T08:46:47Z","timestamp":1614847607000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["The Impact of Gut Microbiome on Metabolic Disorders During Catch-Up Growth in Small-for-Gestational-Age"],"prefix":"10.3389","volume":"12","author":[{"given":"Jingjing","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiya","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.111.6.1253","article-title":"International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001","volume":"111","author":"Lee","year":"2003","journal-title":"Pediatrics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2005.tb01801.x","article-title":"Growth and growth hormone in children born small for gestational age","volume":"94","author":"Rapaport","year":"2005","journal-title":"Acta Paediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4","DOI":"10.6065\/apem.2018.23.1.4","article-title":"Small for gestational age and obesity related comorbidities","volume":"23","author":"Hong","year":"2018","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s13312-015-0588-z","article-title":"Small for gestational age: growth and puberty issues","volume":"52","author":"Yadav","year":"2015","journal-title":"Indian Pediatr"},{"key":"B5","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ghir.2017.12.013","article-title":"Short children born small for gestational age outcomes in the era of growth hormone therapy","volume":"38","author":"Zanelli","year":"2018","journal-title":"Growth Horm IGF Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-0036-z","article-title":"Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children","volume":"48","author":"Mericq","year":"2005","journal-title":"Diabetologia"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.318.7181.427","article-title":"Catch-up growth in childhood and death from coronary heart disease: longitudinal study","volume":"318","author":"Eriksson","year":"1999","journal-title":"Bmj"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.12.2422","article-title":"Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both","volume":"48","author":"Bavdekar","year":"1999","journal-title":"Diabetes"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/1687-9856-2012-12","article-title":"Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder","volume":"2012","author":"Saenger","year":"2012","journal-title":"Int J Pediatr Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199610313351805","article-title":"Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene","volume":"335","author":"Woods","year":"1996","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-11-125","article-title":"Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study","volume":"11","author":"Morgan","year":"2010","journal-title":"BMC Med Genet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2016.1245285","article-title":"Genetic, metabolic and endocrine aspect of intrauterine growth restriction: an update","volume":"30","author":"Sharma","year":"2017","journal-title":"J Matern Fetal Neonatal Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407076101","article-title":"The gut microbiota as an environmental factor that regulates fat storage","volume":"101","author":"Backhed","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.cmet.2017.09.008","article-title":"Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition","volume":"26","author":"Kootte","year":"2017","journal-title":"Cell Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/39.2.338","article-title":"The contribution of the large intestine to energy supplies in man","volume":"39","author":"McNeil","year":"1984","journal-title":"Am J Clin Nutr"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2014.46","article-title":"Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans","volume":"38","author":"Rahat-Rozenbloom","year":"2014","journal-title":"Int J Obes (Lond)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.167","article-title":"Microbiota and SCFA in lean and overweight healthy subjects","volume":"18","author":"Schwiertz","year":"2010","journal-title":"Obes (Silver Spring)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e121","DOI":"10.1038\/nutd.2014.23","article-title":"Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans","volume":"4","author":"Fernandes","year":"2014","journal-title":"Nutr Diabetes"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114512002723","article-title":"Higher level of faecal SCFA in women correlates with metabolic syndrome risk factors","volume":"109","author":"Teixeira","year":"2013","journal-title":"Br J Nutr"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1055\/a-0723-3544","article-title":"Early Growth Hormone Intervention Improves Glucose Metabolism in Adult Rats Born Small for Gestational Age","volume":"128","author":"Wang","year":"2020","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-9-62","article-title":"Peroxisome proliferator-activated receptor gamma modulation and lipogenic response in adipocytes of small-for-gestational age offspring","volume":"9","author":"Yee","year":"2012","journal-title":"Nutr Metab (Lond)"},{"key":"B23","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":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-013-0500-6","article-title":"A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids","volume":"9","author":"Zheng","year":"2013","journal-title":"Metabolomics"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-001-0663-5","article-title":"Evidence of multiple causal sites affecting weight in the IGF2-INS-TH region of human chromosome 11","volume":"110","author":"Gu","year":"2002","journal-title":"Hum Genet"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2012.04496.x","article-title":"Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10-year prospective study","volume":"79","author":"Tsukagawa","year":"2013","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e2142","DOI":"10.7717\/peerj.2142","article-title":"New insight into the role of MMP14 in metabolic balance","volume":"4","author":"Mori","year":"2016","journal-title":"PeerJ"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinmicnews.2008.01.006","article-title":"Lactobacillus: a Review","volume":"30","author":"Slover","year":"2008","journal-title":"Clin Microbiol Newslett"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e31113","DOI":"10.1371\/journal.pone.0031113","article-title":"Effect of Lactobacillus salivarius bacteriocin Abp118 on the mouse and pig intestinal microbiota","volume":"7","author":"Riboulet-Bisson","year":"2012","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7585989","article-title":"Human Gut Microbiota Associated with Obesity in Chinese Children and Adolescents","volume":"2017","author":"Hou","year":"2017","journal-title":"BioMed Res Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2017.161","article-title":"Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials","volume":"41","author":"Crovesy","year":"2017","journal-title":"Int J Obes (Lond)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"fnz254","DOI":"10.1093\/femsle\/fnz254","article-title":"Lactobacillus reuteri A9 and Lactobacillus mucosae A13 isolated from Chinese superlongevity people modulate lipid metabolism in a hypercholesterolemia rat model","volume":"366","author":"Jiang","year":"2019","journal-title":"FEMS Microbiol Lett"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2017.03.021","article-title":"Screening for lactic acid bacteria in traditional fermented Tibetan yak milk and evaluating their probiotic and cholesterol-lowering potentials in rats fed a high-cholesterol diet","volume":"32","author":"Ding","year":"2017","journal-title":"J Funct Foods"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2016.03.006","article-title":"Metabolic role of lactobacilli in weight modification in humans and animals","volume":"106","author":"Drissi","year":"2017","journal-title":"Microb Pathog"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4065\/83.4.460","article-title":"Rittmann BE. Gut microbiota and its possible relationship with obesity","volume":"83","author":"DiBaise","year":"2008","journal-title":"Mayo Clin Proc"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism","volume":"54","author":"den Besten","year":"2013","journal-title":"J Lipid Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"S120","DOI":"10.1097\/MCG.0b013e31822fecfe","article-title":"Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics","author":"Macfarlane","year":"2011","journal-title":"J Clin Gastroenterol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2018.7136","article-title":"Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes","volume":"17","author":"Ji","year":"2019","journal-title":"Exp Ther Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211609200","article-title":"The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids","volume":"278","author":"Brown","year":"2003","journal-title":"J Biol Chem"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301403200","article-title":"Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation","volume":"278","author":"Le Poul","year":"2003","journal-title":"J Biol Chem"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2637002100","article-title":"Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41","volume":"101","author":"Xiong","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.128","article-title":"Short-chain fatty acids in control of body weight and insulin sensitivity","volume":"11","author":"Canfora","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.6.1403","article-title":"Low circulating IGF-II concentrations predict weight gain and obesity in humans","volume":"52","author":"Sandhu","year":"2003","journal-title":"Diabetes"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0819","article-title":"Severe intrauterine growth retardation and atypical diabetes associated with a translocation breakpoint disrupting regulation of the insulin-like growth factor 2 gene","volume":"93","author":"Murphy","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/ng707","article-title":"Paternal transmission of the very common class I INS VNTR alleles predisposes to childhood obesity","volume":"29","author":"Le Stunff","year":"2001","journal-title":"Nat Genet"},{"key":"B47","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/ng0598-98","article-title":"Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood","volume":"19","author":"Dunger","year":"1998","journal-title":"Nat Genet"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0718-2","article-title":"Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of birth weight","volume":"110","author":"Lindsay","year":"2002","journal-title":"Hum Genet"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801927","article-title":"IGF2 genotype and obesity in men and women across the adult age span","volume":"26","author":"Roth","year":"2002","journal-title":"Int J Obes Relat Metab Disord"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.3.848","article-title":"A genomewide linkage scan for abdominal subcutaneous and visceral fat in black and white families: The HERITAGE Family Study","volume":"51","author":"Rice","year":"2002","journal-title":"Diabetes"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.8.807","article-title":"Deletion of a nuclease-sensitive region between the Igf2 and H19 genes leads to Igf2 misregulation and increased adiposity","volume":"10","author":"Jones","year":"2001","journal-title":"Hum Mol Genet"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(03)00231-6","article-title":"Obesity is associated with increased levels of circulating hepatocyte growth factor","volume":"41","author":"Rehman","year":"2003","journal-title":"J Am Coll Cardiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1588","article-title":"Strong association between serum hepatocyte growth factor and metabolic syndrome","volume":"90","author":"Hiratsuka","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-0710","article-title":"Hepatocyte growth factor and clinical diabetes in postmenopausal women","volume":"33","author":"Rajpathak","year":"2010","journal-title":"Diabetes Care"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.630526\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T08:46:49Z","timestamp":1614847609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.630526\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":54,"alternative-id":["10.3389\/fendo.2021.630526"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.630526","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]},"article-number":"630526"}}