puc-header

Multi-Omic Predictors of Steatohepatitis and Advanced Fibrosis in Children

38 Pages Posted: 3 Jan 2019 Sneak Peek Status: Review Complete

See all articles by Kattayoun Kordy

Kattayoun Kordy

University of Southern California - Department of Pediatric Gastroenterology

Fan Li

University of California, Los Angeles (UCLA) - Department of Pediatrics

David J. Lee

University of California, Los Angeles (UCLA) - Department of Pediatrics

Jason M. Kinchen

Metabolon, Inc.

Michael H. Jew

University of Southern California - Department of Pediatrics

Maria Eduarda La Rocque

Universidade do Estado do Rio de Janeiro (UERJ) - Faculty of Medical Sciences

Sofia Martinez

University of El Salvador

Sara Zabih

University of California, Los Angeles (UCLA) - Department of Pediatrics

Monica Saavedra

University of California, Los Angeles (UCLA) - Department of Pediatrics

Cora Woodward

University of California, Los Angeles (UCLA) - Department of Pediatrics

Nicole J. Cunningham

University of California, Los Angeles (UCLA) - Department of Pediatrics

Nicole H. Tobin

University of California, Los Angeles (UCLA) - Department of Pediatrics

Grace M. Aldrovandi

University of California, Los Angeles (UCLA) - Department of Pediatrics

More...

Abstract

Metabolic dysregulation associated with gut microbial dysbiosis can influence the progression of nonalcoholic fatty liver disease (NAFLD) from hepatic steatosis to inflammation and subsequent fibrosis. Using a multi-omics approach, we identified microbiome-derived biochemicals and genes associated with progressive hepatic pathology and fibrosis in Latino children (N=241). Children with more severe liver pathology were dysbiotic and had increased gene content associated with lipopolysaccharide biosynthesis and lipid, amino acid and carbohydrate metabolism. These changes were driven by increases in Bacteroides and concomitant decreases of Akkermansia, Anaerococcus, Corynebacterium, and Finegoldia. Nontargeted mass spectrometry revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. Random forests modeling of plasma metabolites were highly predictive of nonalcoholic steatohepatitis (NASH) (97% accuracy) and hepatic fibrosis, steatosis and lobular inflammation (93.8% accuracy), and can differentiate steatohepatitis from simple steatosis (90.0% accuracy). These metabolomic biomarkers of hepatic pathology provide insights for therapeutic targeting of bacterially-mediated and host pathways.

Keywords: metabolites, 16S rRNA, shotgun, metagenomics, microbiome, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity, children

Suggested Citation

Kordy, Kattayoun and Li, Fan and Lee, David J. and Kinchen, Jason M. and Jew, Michael H. and La Rocque, Maria Eduarda and Martinez, Sofia and Zabih, Sara and Saavedra, Monica and Woodward, Cora and Cunningham, Nicole J. and Tobin, Nicole H. and Aldrovandi, Grace M., Multi-Omic Predictors of Steatohepatitis and Advanced Fibrosis in Children (December 11, 2018). Available at SSRN: https://ssrn.com/abstract=3299431 or http://dx.doi.org/10.2139/ssrn.3299431
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kattayoun Kordy

University of Southern California - Department of Pediatric Gastroenterology

Los Angeles, CA
United States

Fan Li

University of California, Los Angeles (UCLA) - Department of Pediatrics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

David J. Lee

University of California, Los Angeles (UCLA) - Department of Pediatrics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Jason M. Kinchen

Metabolon, Inc.

Morrisville, NC
United States

Michael H. Jew

University of Southern California - Department of Pediatrics

2250 Alcazar Street
Los Angeles, CA 90089
United States

Maria Eduarda La Rocque

Universidade do Estado do Rio de Janeiro (UERJ) - Faculty of Medical Sciences

Rua Tonelero, 380 apt. 804
Copacabana, 22030-000
Brazil

Sofia Martinez

University of El Salvador ( email )

San Salvador
El Salvador

Sara Zabih

University of California, Los Angeles (UCLA) - Department of Pediatrics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Monica Saavedra

University of California, Los Angeles (UCLA) - Department of Pediatrics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Cora Woodward

University of California, Los Angeles (UCLA) - Department of Pediatrics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Nicole J. Cunningham

University of California, Los Angeles (UCLA) - Department of Pediatrics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Nicole H. Tobin

University of California, Los Angeles (UCLA) - Department of Pediatrics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Grace M. Aldrovandi (Contact Author)

University of California, Los Angeles (UCLA) - Department of Pediatrics ( email )

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
217
Downloads
15