Background

Half of obese adolescents with PCOS have hepatic steatosis (HS), the first stage in nonalcoholic fatty liver disease (NAFLD). The gut microbiome is altered in adults with obesity, NAFLD or PCOS and may contribute to worse metabolic outcomes. Whether girls with PCOS, obesity, and HS also have differences in the stool microbiome is unknown.

Methods

Thirty-two obese girls with PCOS +/- HS participated [HS: N=17, age 16.3±0.3 years, BMI 37.7±1.8 kg/m2, hepatic fat 8.9(6.4,18.9)% and NonHS: N=15, age 15.8±0.6, BMI 35.3±1.1, hepatic fat 3.8(2.6,4.3)%]. Participants underwent stool collection, fasting blood collection, an oral glucose tolerance test and MRI for hepatic fat. Fecal bacteria were profiled by high-throughput sequencing of bacterial 16S rRNA gene PCR amplicons (V3V4 region).

Results

Consistent with other NAFLD populations, girls with HS and PCOS had higher transaminases (alanine aminotransferase p=0.003, aspartate aminotransferase p=0.04), glucose concentrations (HbA1c p=0.01; 3-hour glucose p=0.01) and lower insulin sensitivity (Matsuda Index p=0.03). However, the groups showed similar bacterial richness (p=0.296) and evenness (p=0.256). At the phylum level, HS had significantly higher Actinobacteria (13.8%vs 6.4% relative abundance, HS vs. NonHS, p=0.03) and lower Bacteroidetes (5.2% vs 12.9%, p=0.05). At the genus level, HS showed lower %RA of the Firmicutes Faecalibacterium (3.19% vs. 6.75%, p=0.06) and Bacteroidetes spp. (2.9% vs. 7.2%, p=0.07) and theF:B ratio trended to be higher in HS (p=0.09).

Conclusions

Obese adolescents with PCOS and HS have alterations in the gut microbiota at the phylum and genus level, suggesting an interaction of the gut microbiome in HS in PCOS.