Microbiome Signatures Associated with Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease

Abstract Background & Aims The intestinal microbiomemight affect development and severity of nonalcoholic fatty liver disease(NAFLD). We analyzed microbiomesof children with and without NAFLD. Methods We performed a prospective, observational, cross-sectional study of 87 children (8–17 years old) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiomecomposition and functions were assessed using 16S rRNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis. Results Fecal microbiomesof children with NAFLD had lower α-diversity than controls (3.32 vs 3.52; P =.016). Fecal microbiomesfrom children with nonalcoholic steatohepatitis(NASH) had lowest α-diversity (controls, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH 2.97; P = .001). High abundance of Prevotella copriwas associated with more severe fibrosis ( P =.036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomesfrom children NASH ( P P Conclusions In an analysis of fecal microbiomesof children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiomemight contribute to pathogenesis of NAFLD and be used as markers of disease or severity.