{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:39:21Z","timestamp":1775450361890,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD41230"],"award-info":[{"award-number":["HD41230"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD81206"],"award-info":[{"award-number":["HD81206"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"US Department of Veterans' Affairs","award":["IK2CX001717"],"award-info":[{"award-number":["IK2CX001717"]}]},{"DOI":"10.13039\/100018497","name":"UCLA Children's Discovery and Innovation Institute","doi-asserted-by":"publisher","award":["Harry Winston Fellowship"],"award-info":[{"award-number":["Harry Winston Fellowship"]}],"id":[{"id":"10.13039\/100018497","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Intra-Uterine Growth Restriction (IUGR) is a risk factor for many adult-onset chronic diseases, such as diabetes and obesity. These diseases are associated with intestinal microbiome perturbations (dysbiosis). The establishment of an intestinal microbiome begins in utero and continues postnatally (PN). Hypercaloric diet-induced dysbiosis is a major driver of childhood obesity. We hypothesized that different postnatal diets superimposed on IUGR will alter the postnatal intestinal microbiome. We compared four experimental rat groups: (1) Ad lib fed regular chow diet pre- and postnatally (CON), (2\u20133) IUGR induced by maternal caloric restriction prenatally followed postnatally (PN) by either (2) the control diet (IUGR-RC) or (3) High-Fat-high-fructose (IUGR-HFhf) diet, and lastly (4) HFhf ad lib pre- and postnatally (HFhf). Fecal samples were collected from dams and male and female rat offspring at postnatal day 2, 21, and adult day 180 for 16S rRNA gene sequencing. Maternal diet induced IUGR led to dysbiosis of the intestinal microbiome at PN21. Postnatal HFhf diet significantly reduced microbial diversity and worsened dysbiosis reflected by an increased Gammaproteobacteria\/Clostridia ratio. Dysbiosis arising from a mismatch between IUGR and a postnatal HFhf diet may contribute to increased risk of the IUGR offspring for subsequent detrimental health problems.<\/jats:p>","DOI":"10.3390\/nu15010217","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:44:03Z","timestamp":1672627443000},"page":"217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Variation in the Early Life and Adult Intestinal Microbiome of Intra-Uterine Growth Restricted Rat Offspring Exposed to a High Fat and Fructose Diet"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4155-5390","authenticated-orcid":false,"given":"Liesbeth V.","family":"Maggiotto","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology & Developmental Biology and UCLA Children\u2019s Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-5850","authenticated-orcid":false,"given":"Shubhamoy","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology & Developmental Biology and UCLA Children\u2019s Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Chul","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology & Developmental Biology and UCLA Children\u2019s Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology & Developmental Biology and UCLA Children\u2019s Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6500-8255","authenticated-orcid":false,"given":"Venu","family":"Lagishetty","sequence":"additional","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"},{"name":"Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-0254","authenticated-orcid":false,"given":"Jonathan P.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"The Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"},{"name":"Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherin U.","family":"Devaskar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology & Developmental Biology and UCLA Children\u2019s Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nature09944","article-title":"Enterotypes of the human gut microbiome","volume":"473","author":"Arumugam","year":"2011","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1152\/physiol.00033.2015","article-title":"Intrauterine Growth Restriction: Hungry for an Answer","volume":"31","author":"Devaskar","year":"2016","journal-title":"Physiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1007\/s12098-012-0834-5","article-title":"Fetal programming and the risk of noncommunicable disease","volume":"80","author":"Fall","year":"2013","journal-title":"Indian J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"020405","DOI":"10.7189\/jogh.09.020405","article-title":"The impact of maternal nutrition on offspring\u2019s risk of non-communicable diseases in adulthood: A systematic review","volume":"9","author":"Pullar","year":"2019","journal-title":"J. Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S2213-8587(14)70134-2","article-title":"Obesity, inflammation, and the gut microbiota","volume":"3","author":"Cox","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lecomte, V., Kaakoush, N.O., Maloney, C.A., Raipuria, M., Huinao, K.D., Mitchell, H.M., and Morris, M.J. (2015). Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126931"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1038\/ncomms4889","article-title":"High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model","volume":"5","author":"Ma","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1001\/jamapediatrics.2015.3732","article-title":"Association of Cesarean Delivery and Formula Supplementation with the Intestinal Microbiome of 6-Week-Old Infants","volume":"170","author":"Madan","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1113\/jphysiol.2009.174136","article-title":"The core gut microbiome, energy balance and obesity","volume":"587","author":"Turnbaugh","year":"2009","journal-title":"J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.21307\/ane-2017-033","article-title":"Energy-dense diet triggers changes in gut microbiota, reorganization of gut-brain vagal communication and increases body fat accumulation","volume":"77","author":"Vaughn","year":"2017","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15718","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":"ref_12","doi-asserted-by":"crossref","first-page":"1027","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":"ref_13","doi-asserted-by":"crossref","first-page":"5605","DOI":"10.2527\/jas.2013-6824","article-title":"Intrauterine growth restricted piglets defined by their head shape ingest insufficient amounts of colostrum","volume":"91","author":"Amdi","year":"2013","journal-title":"J. Anim. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s40104-019-0397-7","article-title":"Maternal imprinting of the neonatal microbiota colonization in intrauterine growth restricted piglets: A review","volume":"10","author":"Jiang","year":"2019","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fped.2019.00099","article-title":"Characteristics of the Intestinal Microbiota in Very Low Birth Weight Infants With Extrauterine Growth Restriction","volume":"7","author":"Li","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4216","DOI":"10.1210\/en.2012-1206","article-title":"Superimposition of postnatal calorie restriction protects the aging male intrauterine growth- restricted offspring from metabolic maladaptations","volume":"153","author":"Dai","year":"2012","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.2337\/db11-1347","article-title":"Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity","volume":"61","author":"Garg","year":"2012","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1002\/jnr.23013","article-title":"Pre- and postnatal calorie restriction perturbs early hypothalamic neuropeptide and energy balance","volume":"90","author":"Shin","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1073\/pnas.1000080107","article-title":"Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample","volume":"108","author":"Caporaso","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/0471142735.im0741s107","article-title":"Sampling of intestinal microbiota and targeted amplification of bacterial 16S rRNA genes for microbial ecologic analysis","volume":"107","author":"Tong","year":"2014","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"852","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":"ref_22","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"McMurdie, P.J., and Holmes, S. (2013). phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061217"},{"key":"ref_24","unstructured":"Ernst, F.S.S., Borman, T., and Lahti, L. (2022). mia: Microbiome Analysis, R Package Version 1.6.0."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.1038\/s41467-020-17041-7","article-title":"Analysis of compositions of microbiomes with bias correction","volume":"11","author":"Lin","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32484","DOI":"10.1038\/srep32484","article-title":"High fat diet drives obesity regardless the composition of gut microbiota in mice","volume":"6","author":"Rabot","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.cmet.2016.05.001","article-title":"Altered Microbiota Contributes to Reduced Diet-Induced Obesity upon Cold Exposure","volume":"23","author":"Zietak","year":"2016","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100508","DOI":"10.1016\/j.nmni.2019.01.004","article-title":"Anaerotruncus massiliensis sp. nov., a succinate-producing bacterium isolated from human stool from an obese patient after bariatric surgery","volume":"29","author":"Togo","year":"2019","journal-title":"New Microbes New Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.nutres.2016.08.001","article-title":"Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction","volume":"36","author":"Chu","year":"2016","journal-title":"Nutr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1210\/en.2016-1259","article-title":"Maternal Calorie Restriction Causing Uteroplacental Insufficiency Differentially Affects Mammalian Placental Glucose and Leucine Transport Molecular Mechanisms","volume":"157","author":"Ganguly","year":"2016","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1096\/fj.08-116889","article-title":"High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57\/BL6 mice","volume":"23","author":"Jones","year":"2009","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"736944","DOI":"10.3389\/fnut.2021.736944","article-title":"Maternal Obesity Related to High Fat Diet Induces Placenta Remodeling and Gut Microbiome Shaping That Are Responsible for Fetal Liver Lipid Dysmetabolism","volume":"8","author":"Wang","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.3389\/fmicb.2017.01221","article-title":"The Gut Microbiota of Healthy Chilean Subjects Reveals a High Abundance of the Phylum Verrucomicrobia","volume":"8","author":"Vasquez","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12674","DOI":"10.1038\/s41598-019-49081-5","article-title":"Expression of immune regulatory genes correlate with the abundance of specific Clostridiales and Verrucomicrobia species in the equine ileum and cecum","volume":"9","author":"Lindenberg","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.nutres.2019.08.004","article-title":"Early life high-fat diet exposure maintains glucose tolerance and insulin sensitivity with a fatty liver and small brain size in the adult offspring","volume":"69","author":"Shin","year":"2019","journal-title":"Nutr. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Magne, F., Gotteland, M., Gauthier, L., Zazueta, A., Pesoa, S., Navarrete, P., and Balamurugan, R. (2020). The Firmicutes\/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?. Nutrients, 12.","DOI":"10.3390\/nu12051474"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"606490","DOI":"10.3389\/fcimb.2021.606490","article-title":"A Comparison Study of Age and Colorectal Cancer-Related Gut Bacteria","volume":"11","author":"Zhang","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mariat, D., Firmesse, O., Levenez, F., Guimaraes, V., Sokol, H., Dore, J., Corthier, G., and Furet, J.P. (2009). The Firmicutes\/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-123"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.chom.2019.06.013","article-title":"Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet","volume":"26","author":"Bisanz","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/4441022a","article-title":"Microbial ecology: Human gut microbes associated with obesity","volume":"444","author":"Ley","year":"2006","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"190","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":"Obesity"},{"key":"ref_42","first-page":"308","article-title":"The human gut microbiota: Metabolism and perspective in obesity","volume":"9","author":"Gomes","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene expression omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/1\/217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:55:43Z","timestamp":1760118943000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/1\/217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["nu15010217"],"URL":"https:\/\/doi.org\/10.3390\/nu15010217","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,1]]}}}