• Ayesha Monga Kravetz, Todd Testerman, Brittany Galuppo, Joerg Graf, Bridget Pierpont, Stephan Siebel, Richard Feinn, and Nicola Santoro.
• Frank H. Netter MD School of Medicine, North Haven, Connecticut.
• J. Clin. Endocrinol. Metab. 2020 Oct 1; 105 (10).

ContextNonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, affecting approximately 3 in 10 obese children worldwide.ObjectiveWe aimed to investigate the potential relationship between gut microbiota and NAFLD in obese youth, while considering the role of PNPLA3 rs738409, a strong genetic contributor to NAFLD.DesignIn this cross-sectional study, participants completed an abdominal magnetic resonance imaging to measure hepatic fat fraction (HFF), oral glucose tolerance test, and PNPLA3 rs738409 genotyping. Fecal samples were collected to analyze the V4 region of the 16S rRNA gene for intestinal bacteria characterization.SettingYale Pediatric Obesity Clinic.ParticipantsObese youth (body mass index >95th percentile) with NAFLD (HFF ≥5.5%; n = 44) and without NAFLD (HFF <5.5%; n = 29).Main Outcome MeasureShannon-Wiener diversity index values and proportional bacterial abundance by NAFLD status and PNPLA3 genotype.ResultsSubjects with NAFLD had decreased bacterial alpha-diversity compared with those without NAFLD (P = 0.013). Subjects with NAFLD showed a higher Firmicutes to Bacteroidetes (F/B) ratio (P = 0.019) and lower abundance of Bacteroidetes (P = 0.010), Prevotella (P = 0.019), Gemmiger (P = 0.003), and Oscillospira (P = 0.036). F/B ratio, Bacteroidetes, Gemmiger, and Oscillospira were associated with HFF when controlling for group variations. We also observed an additive effect on HFF by PNPLA3 rs738409 and Gemmiger, and PNPLA3 rs738409 and Oscillospira.ConclusionsObese youth with NAFLD have a different gut microbiota composition than those without NAFLD. These differences were still statistically significant when controlling for factors associated with NAFLD, including PNPLA3 rs738409.© Endocrine Society 2020.

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