title: Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease.
abstract: Obesity is becoming the new pediatric epidemic. Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity and has become the most common cause of pediatric liver disease. The gut microbiome is the major metabolic organ and determines how calories are processed, serving as a caloric gate and contributing towards the pathogenesis of NAFLD. The goal of this study is to examine gut microbial profiles in children with NAFLD using phylogenetic, metabolomic, metagenomic and proteomic approaches. Fecal samples were obtained from obese children with or without NAFLD and healthy lean children. Stool specimens were subjected to 16S rRNA gene microarray, shotgun sequencing, mass spectroscopy for proteomics and NMR spectroscopy for metabolite analysis. Children with NAFLD had more abundant Gammaproteobacteria and Prevotella and significantly higher levels of ethanol, with differential effects on short chain fatty acids. This group also had increased genomic and protein abundance for energy production with a reduction in carbohydrate and amino acid metabolism and urea cycle and urea transport systems. The metaproteome and metagenome showed similar findings. The gut microbiome in pediatric NAFLD is distinct from lean healthy children with more alcohol production and pathways allocated to energy metabolism over carbohydrate and amino acid metabolism, which would contribute to development of disease.
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition at Children's Hospital Los Angeles, 4650 Sunset Blvd. MS#78, Los Angeles, CA 90027, USA Keck School of Medicine at the University of Southern California, Los Angeles, CA 90089, USA sonia.michail@hotmail.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Michail
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition at Children's Hospital Los Angeles, 4650 Sunset Blvd. MS#78, Los Angeles, CA 90027, USA Keck School of Medicine at the University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Malinda
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition at Children's Hospital Los Angeles, 4650 Sunset Blvd. MS#78, Los Angeles, CA 90027, USA Keck School of Medicine at the University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Frey
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition at Children's Hospital Los Angeles, 4650 Sunset Blvd. MS#78, Los Angeles, CA 90027, USA Childrens Hospital Los Angeles Proteomics Core, 4650 Sunset Blvd. MS#78, Los Angeles, CA 90027, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Fanter
authors.affiliation: Department of Biochemistry & Molecular Biology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Paliy
authors.affiliation: Real time Genomics, 999 Bayhill Dr #101, San Bruno, CA 94066, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Hilbush
authors.affiliation: Department of Biochemistry & Molecular Biology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA.
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Reo
mesh_terms: D000293:Adolescent; D002648:Child; D004734:Energy Metabolism / Q000502:physiology*; D000431:Ethanol / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D020563:Gammaproteobacteria / Q000235:genetics; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008297:Male; D054892:Metagenome / Q000235:genetics; D064307:Microbiota / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010802:Phylogeny; D018720:Prevotella / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D012336:RNA, Ribosomal, 16S; D000431:Ethanol
keywords: NASH; carbohydrate; energy metabolism; gut microbiome; obesity