{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:49:16Z","timestamp":1790196556228,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092993\/Z\/10\/Z"],"award-info":[{"award-number":["092993\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR200254"],"award-info":[{"award-number":["NIHR200254"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>Children of mothers with intrahepatic cholestasis of pregnancy (ICP) are more likely to develop metabolic disease later in life. Using a mouse model of gestational cholestasis, we previously found that 18-week-old offspring had metabolic alterations that were exacerbated in female offspring when challenged with a Western diet (WD). Microbiota changes are emerging as a potential mechanism for developmental programming, and the maternal gut microbiota is known to be altered in pregnancy and in ICP. We hypothesized that, in our model, the offspring gut microbiota is altered by maternal gestational disease, potentially impacting future offspring metabolic health. Female mice were fed a cholic acid (CA)-supplemented diet for 1\u00a0week preceding and throughout pregnancy to mimic gestational hypercholanemia. Female offspring were challenged with a WD from 12 to 18\u00a0weeks of age and cecal contents were collected for metataxonomics and metabolomic profiling. Maternal CA dietary supplementation was associated with markedly increased cecal sulfated bile acid species (up to 387-fold increase). Whilst WD-feeding of offspring was associated with a greater proportion of primary to secondary bile acids, and more tauro-conjugated bile acids than for offspring fed a normal diet, this adaptation to WD-feeding was not evident for those whose mothers were fed a CA-supplemented diet. Indeed, WD-fed offspring of CA-supplemented mothers had a &amp;gt;2-fold reduction in CA and dehydrocholic acid levels compared to those from NC-fed mothers. This corresponded with an altered profile of cecal microbiota, with clear separation of microbiotal profiles according to maternal diet in the WD-fed, but not NC-fed, offspring. This observational mouse study has shown that exposure to maternal hypercholanemia can significantly impact the effects of an obesogenic diet on offspring intestinal bile acid metabolism and gut microbiota, likely increasing their vulnerability to metabolic dysfunction when exposed to the \u201csecond hit\u201d of an unhealthy postnatal environment.<\/jats:p>","DOI":"10.3389\/ebm.2026.10810","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T10:54:56Z","timestamp":1769770496000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Maternal diet-induced hypercholanemia alters gut microbiota and metabolome in adult female Western diet-fed offspring"],"prefix":"10.3389","volume":"251","author":[{"given":"Caroline","family":"Ovadia","sequence":"first","affiliation":[{"name":"Department of Women and Children\u2019s Health, King\u2019s College London","place":["London, United Kingdom"]},{"name":"Centre for Reproductive Health, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saraid","family":"McIlvride","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josca M.","family":"Schoonejans","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Spagou","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"G\u00f3mez-Romero","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Health and Social Wellbeing, University West of England","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Papacleovoulou","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanya","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian R.","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Women and Children\u2019s Health, King\u2019s College London","place":["London, United Kingdom"]},{"name":"Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100941","DOI":"10.1016\/j.mam.2021.100941","article-title":"Nuclear receptors, gestational metabolism and maternal metabolic disorders","volume":"78","author":"Manna","year":"2021","journal-title":"Mol Aspects Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.ejogrb.2018.10.041","article-title":"Intrahepatic cholestasis of pregnancy: review of six national and regional guidelines","volume":"231","author":"Bicocca","year":"2018","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/S0140-6736(18)31877-4","article-title":"Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses","volume":"393","author":"Ovadia","year":"2019","journal-title":"The Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ejogrb.2013.12.037","article-title":"Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes","volume":"176","author":"Martineau","year":"2014","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1172\/JCI68927","article-title":"Maternal cholestasis during pregnancy programs metabolic disease in offspring","volume":"123","author":"Papacleovoulou","year":"2013","journal-title":"J Clin Invest"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0175675","DOI":"10.1371\/journal.pone.0175675","article-title":"Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations","volume":"12","author":"Wankhade","year":"2017","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","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":"B8","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.chom.2018.06.005","article-title":"Mother-to-Infant microbial transmission from different body sites shapes the developing infant gut microbiome","volume":"24","author":"Ferretti","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1796S","DOI":"10.1093\/jn\/138.9.1796S","article-title":"Cesarean delivery may affect the early biodiversity of intestinal bacteria","volume":"138","author":"Biasucci","year":"2008","journal-title":"J Nutr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"11971","DOI":"10.1073\/pnas.1002601107","article-title":"Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns","volume":"107","author":"Dominguez-Bello","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4997","DOI":"10.1038\/s41467-019-13014-7","article-title":"Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life","volume":"10","author":"Reyman","year":"2019","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1002\/hep.30661","article-title":"Enhanced microbial bile acid deconjugation and impaired ileal uptake in pregnancy repress intestinal regulation of bile acid synthesis","volume":"70","author":"Ovadia","year":"2019","journal-title":"Hepatology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1186\/s12876-020-01510-w","article-title":"Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy","volume":"20","author":"Li","year":"2020","journal-title":"BMC Gastroenterol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"7338","DOI":"10.3748\/wjg.v26.i46.7338","article-title":"Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients","volume":"26","author":"Li","year":"2020","journal-title":"World J Gastroenterol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"635680","DOI":"10.3389\/fcimb.2021.635680","article-title":"Alterations of the human gut microbiota in intrahepatic cholestasis of pregnancy","volume":"11","author":"Zhan","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3895","DOI":"10.1038\/s41598-020-60821-w","article-title":"Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing bacteroidetes in cholestatic pregnancy","volume":"10","author":"Ovadia","year":"2020","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1080\/19490976.2017.1408763","article-title":"Removal of the cecum affects intestinal fermentation, enteric bacterial community structure, and acute colitis in mice","volume":"9","author":"Brown","year":"2018","journal-title":"Gut Microbes"},{"key":"B18","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1152\/ajpgi.00336.2009","article-title":"The normal mechanisms of pregnancy-induced liver growth are not maintained in mice lacking the bile acid sensor fxr","volume":"298","author":"Milona","year":"2010","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/nprot.2012.135","article-title":"Global metabolic profiling of animal and human tissues via UPLC-MS","volume":"8","author":"Want","year":"2013","journal-title":"Nat Protoc"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4184","DOI":"10.1021\/ac503775m","article-title":"Untargeted UPLC-MS profiling pipeline to expand tissue metabolome coverage: application to cardiovascular disease","volume":"87","author":"Vorkas","year":"2015","journal-title":"Anal Chem"},{"key":"B21","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1021\/ac102523q","article-title":"HILIC-UPLC-MS for exploratory urinary metabolic profiling in toxicological studies","volume":"83","author":"Spagou","year":"2011","journal-title":"Anal Chem"},{"key":"B22","doi-asserted-by":"publisher","first-page":"9662","DOI":"10.1021\/acs.analchem.5b01556","article-title":"Bile acid profiling and quantification in biofluids using ultra-performance liquid chromatography tandem mass spectrometry","volume":"87","author":"Sarafian","year":"2015","journal-title":"Anal Chem"},{"key":"B23","unstructured":"R: a language and environment for statistical computing\n          \n          \n          2018"},{"key":"B24","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jaut.2014.03.005","article-title":"Long term effect of gut microbiota transfer on diabetes development","volume":"53","author":"Peng","year":"2014","journal-title":"J Autoimmun"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e27310","DOI":"10.1371\/journal.pone.0027310","article-title":"Reducing the effects of PCR amplification and sequencing artifacts on 16S rRNA-Based studies","volume":"6","author":"Schloss","year":"2011","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Na\u00efve Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl Environ Microbiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1093\/bioinformatics\/btu494","article-title":"STAMP: statistical analysis of taxonomic and functional profiles","volume":"30","author":"Parks","year":"2014","journal-title":"Bioinformatics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1111\/1471-0528.17798","article-title":"Serum bile acid measurements in women of European and South Asian ethnicity with or without gestational diabetes mellitus: a cohort study","volume":"131","author":"Schoonejans","year":"2024","journal-title":"BJOG"},{"key":"B29","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1093\/nutrit\/nux053","article-title":"Developmental origins of health and disease: current knowledge and potential mechanisms","volume":"75","author":"Hoffman","year":"2017","journal-title":"Nutr Rev"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e14694","DOI":"10.1111\/dme.14694","article-title":"Developmental programming by maternal obesity: lessons from animal models","volume":"38","author":"Schoonejans","year":"2021","journal-title":"Diabetic Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"R85","DOI":"10.1530\/REP-21-0241","article-title":"Gestational microbiome: metabolic perturbations and developmental programming","volume":"162","author":"Han","year":"2021","journal-title":"Reproduction"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1080\/14767058.2018.1506760","article-title":"Changes of intestinal microbiota in early life","volume":"33","author":"Ficara","year":"2020","journal-title":"J Maternal-Fetal Neonatal Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e92","DOI":"10.1542\/peds.2014-0596","article-title":"Cesarean section chronic immune disorders","volume":"135","author":"Sevelsted","year":"2015","journal-title":"Pediatrics"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e794","DOI":"10.1542\/peds.2011-3886","article-title":"Antibiotic exposure and IBD development among children: a population-based cohort study","volume":"130","author":"Kronman","year":"2012","journal-title":"Pediatrics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.2337\/dbi17-0011","article-title":"Developmental programming of obesity and diabetes in mouse, monkey, and man in 2018: where are we headed?","volume":"67","author":"Friedman","year":"2018","journal-title":"Diabetes"},{"key":"B36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s40168-019-0689-3","article-title":"Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease","volume":"7","author":"Heinken","year":"2019","journal-title":"Microbiome"},{"key":"B37","doi-asserted-by":"publisher","first-page":"889646","DOI":"10.3389\/fimmu.2022.889646","article-title":"Intrahepatic cholestasis of pregnancy increases inflammatory susceptibility in neonatal offspring by modulating gut microbiota","volume":"13","author":"Lin","year":"2022","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"G295","DOI":"10.1152\/ajpgi.00247.2021","article-title":"Maternal obesogenic diet regulates offspring bile acid homeostasis and hepatic lipid metabolism via the gut microbiome in mice","volume":"322","author":"Thompson","year":"2022","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.cmet.2013.01.003","article-title":"Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist","volume":"17","author":"Sayin","year":"2013","journal-title":"Cell Metab"},{"key":"B40","doi-asserted-by":"publisher","first-page":"889040","DOI":"10.3389\/fnut.2022.889040","article-title":"Effects of probiotic intervention on markers of inflammation and health outcomes in women of reproductive age and their children","volume":"9","author":"Kwok","year":"2022","journal-title":"Front Nutr"}],"container-title":["Experimental Biology and Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.ebm-journal.org\/articles\/10.3389\/ebm.2026.10810\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T10:54:58Z","timestamp":1769770498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ebm-journal.org\/articles\/10.3389\/ebm.2026.10810\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":40,"alternative-id":["10.3389\/ebm.2026.10810"],"URL":"https:\/\/doi.org\/10.3389\/ebm.2026.10810","relation":{},"ISSN":["1535-3699"],"issn-type":[{"value":"1535-3699","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"article-number":"10810"}}