ABSTRACT
OBJECTIVE: 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. METHODS: 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. RESULTS: 50% had HS (N = 17, age 16.2±1.5 years, BMI 38±7 kg/m2, HFF 9.8[6.5, 20.7]%) and 50% did not (N = 17, age 15.8±2.2 years, BMI 35±4 kg/m2, HFF 3.8[2.6, 4.4]%). The groups showed no difference in bacterial α-diversity (richness p = 0.202; evenness p = 0.087; and diversity p = 0.069) or global difference in microbiota (ß-diversity). Those with HS had lower % relative abundance (%RA) of Bacteroidetes (p = 0.013), Bacteroidaceae (p = 0.009), Porphyromonadaceae (p = 0.011), and Ruminococcaceae (p = 0.008), and higher Firmicutes:Bacteroidetes (F:B) ratio (47.8% vs. 4.3%, p = 0.018) and Streptococcaceae (p = 0.034). Bacterial taxa including phyla F:B ratio, Bacteroidetes, and family Bacteroidaceae, Ruminococcaceae and Porphyromonadaceae correlated with metabolic markers. CONCLUSIONS: 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.
Subject(s)
Fatty Liver/pathology , Gastrointestinal Microbiome , Obesity/pathology , Polycystic Ovary Syndrome/pathology , Adolescent , Bacteroidetes/genetics , Bacteroidetes/isolation & purification , Blood Glucose/analysis , Cross-Sectional Studies , Fatty Liver/complications , Fatty Liver/diagnostic imaging , Feces/microbiology , Female , Firmicutes/genetics , Firmicutes/isolation & purification , Glucose Tolerance Test , Humans , Magnetic Resonance Imaging , Obesity/complications , Polycystic Ovary Syndrome/complications , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Young AdultABSTRACT
CONTEXT: Alterations in gut microbiota relate to the metabolic syndrome, but have not been examined in at-risk obese youth with polycystic ovary syndrome (PCOS). OBJECTIVE: Compare the composition and diversity of the gut microbiota and associations with metabolic and hormonal measures between 2 groups of female adolescents with equal obesity with or without PCOS. DESIGN: Prospective, case-control cross-sectional study. SETTING: Tertiary-care center. PARTICIPANTS: A total of 58 obese female adolescents (n = 37 with PCOS; 16.1 ± 0.3 years of age; body mass index [BMI] 98.5th percentile) and (n = 21 without PCOS; 14.5 ± 0.4 years of age; BMI 98.7th percentile). OUTCOMES: Bacterial diversity, percent relative abundance (%RA), and correlations with hormonal and metabolic measures. RESULTS: Participants with PCOS had decreased α-diversity compared with the non-PCOS group (Shannon diversity P = 0.045 and evenness P = 0.0052). ß-diversity, reflecting overall microbial composition, differed between groups (P < 0.001). PCOS had higher %RA of phyla Actinobacteria (P = 0.027), lower Bacteroidetes (P = 0.004), and similar Firmicutes and Proteobacteria. PCOS had lower %RA of families Bacteroidaceae (P < 0.001) and Porphyromonadaceae (P = 0.024) and higher Streptococcaceae (P = 0.047). Lower bacterial α-diversity was strongly associated with higher testosterone concentrations. Several individual taxa correlated with testosterone and metabolic measures within PCOS and across the entire cohort. Receiver operative curve analysis showed 6 taxa for which the %RA related to PCOS status and lower Bacteroidaceae conferred a 4.4-fold likelihood ratio for PCOS. CONCLUSION: Alterations in the gut microbiota exist in obese adolescents with PCOS versus obese adolescents without PCOS and these changes relate to markers of metabolic disease and testosterone. Further work is needed to determine if microbiota changes are reflective of, or influencing, hormonal metabolism.
