{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:16:23Z","timestamp":1780589783162,"version":"3.54.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["K23DK107871"],"award-info":[{"award-number":["K23DK107871"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","award":["2015212"],"award-info":[{"award-number":["2015212"]}],"id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005508","name":"Boettcher Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005508","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Colorado GI & Liver Innate Immune Program"},{"name":"University of Colorado GI & Liver Innate Immune Program"},{"name":"University of Colorado GI & Liver Innate Immune Program"},{"name":"University of Colorado GI & Liver Innate Immune Program"},{"name":"Center for Women\u2019s Health Research"},{"name":"NIH\/NCATS Colorado CTSA","award":["UL1 TR002535"],"award-info":[{"award-number":["UL1 TR002535"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Hepatic steatosis (HS) is common in adolescents with obesity and polycystic ovary syndrome (PCOS). Gut microbiota are altered in adults with obesity, HS, and PCOS, which may worsen metabolic outcomes, but similar data is lacking in youth.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Thirty-four adolescents with PCOS and obesity underwent stool and fasting blood collection, oral glucose tolerance testing, and MRI for hepatic fat fraction (HFF). Fecal bacteria were profiled by high-throughput 16S rRNA gene sequencing.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>50% had HS (N = 17, age 16.2\u00b11.5 years, BMI 38\u00b17 kg\/m<jats:sup>2<\/jats:sup>, HFF 9.8[6.5, 20.7]%) and 50% did not (N = 17, age 15.8\u00b12.2 years, BMI 35\u00b14 kg\/m<jats:sup>2<\/jats:sup>, HFF 3.8[2.6, 4.4]%). The groups showed no difference in bacterial \u03b1-diversity (richness p = 0.202; evenness p = 0.087; and diversity p = 0.069) or global difference in microbiota (\u03b2-diversity). Those with HS had lower % relative abundance (%RA) of <jats:italic>Bacteroidetes<\/jats:italic> (p = 0.013), <jats:italic>Bacteroidaceae<\/jats:italic> (p = 0.009), <jats:italic>Porphyromonadaceae<\/jats:italic> (p = 0.011), and <jats:italic>Ruminococcaceae<\/jats:italic> (p = 0.008), and higher <jats:italic>Firmicutes<\/jats:italic>:<jats:italic>Bacteroidetes (F<\/jats:italic>:<jats:italic>B)<\/jats:italic> ratio (47.8% vs. 4.3%, p = 0.018) and <jats:italic>Streptococcaceae<\/jats:italic> (p = 0.034). Bacterial taxa including phyla <jats:italic>F<\/jats:italic>:<jats:italic>B<\/jats:italic> ratio, <jats:italic>Bacteroidetes<\/jats:italic>, and family <jats:italic>Bacteroidaceae<\/jats:italic>, <jats:italic>Ruminococcaceae<\/jats:italic> and <jats:italic>Porphyromonadaceae<\/jats:italic> correlated with metabolic markers.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Obese adolescents with PCOS and HS have differences in composition of gut microbiota, which correlate with metabolic markers, suggesting a modifying role of gut microbiota in HS and PCOS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0245219","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T18:28:19Z","timestamp":1611080899000},"page":"e0245219","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hepatic steatosis relates to gastrointestinal 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Matthews","year":"1985","journal-title":"Diabetologia"},{"issue":"9","key":"pone.0245219.ref036","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp","volume":"22","author":"M Matsuda","year":"1999","journal-title":"Diabetes care"},{"issue":"23","key":"pone.0245219.ref037","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1093\/bioinformatics\/btt526","article-title":"Explicet: graphical user interface software for metadata-driven management, analysis and visualization of microbiome data","volume":"29","author":"CE Robertson","year":"2013","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0245219.ref038","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/hep.26093","article-title":"Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between 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