Hepatic steatosis relates to gastrointestinal microbiota changes in obese girls with polycystic ovary syndrome

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 (β-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.

Fig 1. Alpha biodiversity measures.

Measures of α-biodiversity including: A) Richness (Chao1) B) Evenness (Shannon H/Hmax), C) Shannon diversity (Shannon H). There were no statistical differences in α- and β-diversity between groups.

Fig 2. Percent relative abundance in HS and No-HS.

Manhattan plot of bacterial %RA between groups at the A) Phyla B) Family and C) Genus level. Only taxa with > 1% RA are included. Lines above 0 are >%RA in HS and below 0 >%RA in No-HS, with dotted horizontal lines representing p<0.05 and p<0.01. HS had higher %RA of Firmicutes:Bacteroidetes ratio and lower Bacteroidetes. At the family level, HS had higher %RA of Streptococcaceae, and lower Bacteroidaceae, Porphyromonadaceae, and Ruminococcaceae. At the genus level, HS had higher %RA of Streptococcus and Anaerostipes, and lower %RA of Bacteroides, Faecalibacterium and Ruminococcaceae.