{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:03:17Z","timestamp":1780408997792,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"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. Physiol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The gut microbiome is altered in obese adolescents with polycystic ovary syndrome (PCOS), and is associated with free testosterone, metabolic markers, and insulin resistance. Combined oral contraceptives (OCP) are a primary treatment for PCOS and decrease testosterone, but the effect on the serum metabolome or gut microbiome in obese adolescents with PCOS is unknown.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> Contrast gut microbiome profiles, targeted serum metabolomics, hormone levels, and metabolic measures in adolescents with PCOS and obesity with and without OCP treatment.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Adolescent girls with obesity and PCOS underwent stool and fasting blood collection and MRI for hepatic fat fraction. Fecal bacteria were profiled by high-throughput 16S rRNA gene sequencing and fasting serum metabolomics performed with high resolution mass spectrometry. Groups were contrasted using t-tests and principle least squares discrimination analysis (PLS-DA). Associations between bacterial taxa, baseline metabolic measures, hormone levels and the metabolome were conducted using Spearman analysis. Analyses were adjusted for false discovery rate.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> 29 adolescents with obesity [Untreated N = 21, 16 \u00b1 1.2\u00a0years, BMI%ile 36.5 \u00b1 3.0; OCP N = 8, 15.5 \u00b1 0.9\u00a0years, BMI%ile 32.5 \u00b1 3.9] participated. Of the untreated adolescents, N = 14 contributed serum for metabolomic analysis. Participants on OCP therapy had lower free testosterone and free androgen index (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) and higher sex hormone binding globulin. There was no difference in measures of fasting glucose, insulin, lipids or HOMA-IR between groups. PLS-DA of serum metabolomics showed discrimination between the groups, secondary amino acid changes. Untreated and OCP had similar stool microbiome \u03b1-diversity based on evenness (<jats:italic>p<\/jats:italic> = 0.28), richness (<jats:italic>p<\/jats:italic> = 0.39), and Shannon diversity (<jats:italic>p<\/jats:italic> = 0.24) and global microbial composition (\u03b2-diversity, <jats:italic>p<\/jats:italic> = 0.56). There were no differences in % relative abundance at any level. Bacterial \u03b1-diversity was negatively associated with serum long chain fatty acids and branched chain amino acids. A higher %relative abundance of family Ruminococcaceae was significantly associated with serum bile acids and HOMA-IR.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Despite hormone and serum amino acid differences, girls treated with OCP had similar metabolic and gut microbiome profiles compared to the untreated PCOS group. The association between bacterial \u03b1-diversity, Ruminococcaceae, clinical markers and long chain fatty acids suggests a potential role of the gut microbiome in the pathogenesis of the metabolic comorbidities in PCOS.<\/jats:p>","DOI":"10.3389\/fphys.2022.887077","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T15:29:56Z","timestamp":1655825396000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Combined Oral Contraceptive Treatment Does Not Alter the Gut Microbiome but Affects Amino Acid Metabolism in Sera of Obese Girls With Polycystic Ovary Syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Beza","family":"Tayachew","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Vanden Brink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesenia","family":"Garcia-Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haseeb","family":"Rahat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"D'Alessandro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N.","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Silveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Kelsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Cree-Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11061356","article-title":"Glycine Metabolism and its Alterations in Obesity and Metabolic Diseases","volume":"11","author":"Alves","year":"2019","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"bvab008","DOI":"10.1210\/jendso\/bvab008","article-title":"Racial and Ethnic Differences in Metabolic Disease in Adolescents with Obesity and Polycystic Ovary Syndrome","volume":"5","author":"Andrisse","year":"2021","journal-title":"J. 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