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RCT·pediatrics, gastroenterology, nutrition, clinical trial, endocrinology·PMC10053986

Metabolome × Microbiome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys

Metabolites · 11 authors, 10 centres

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TL;DR

This randomized controlled trial in adolescent boys with nonalcoholic fatty liver disease (NAFLD) found that an 8-week low free-sugar diet, compared to a usual diet, was associated with specific changes in blood metabolites and gut microbes, alongside a reduction in liver fat.

Full summary

887 CHARS

This 8-week randomized controlled trial assessed metabolome and microbiome changes in 40 adolescent boys with NAFLD randomized to a low free-sugar diet (n=20) or usual diet (n=20). The diet group showed differential expression of metabolite features enriched in amino acid and lipid pathways, with specific increases in serine, glycine, 2-aminobutyric acid, and 3-hydroxybutyric acid, and a decrease in linolenic acid. The diet group also had a greater mean decrease in hepatic fat (25% to 17%) compared to the control group (21% to 20.0%). Limitations include the homogenous sample limiting generalizability, potential underpowering as a pilot study, and the inability to distinguish whether findings were due to reduced sugar intake or hepatic fat loss. The findings provide insight into potential biological mechanisms and response biomarkers but require validation in larger studies.

STUDY TYPE

RCT

SPECIALTY

pediatrics

SUMMARISED BY

AI pipeline

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100% · A

ORIGINAL PAPER

PMC10053986

Metabolome × Microbiome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys

Metabolites

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ABSTRACT

Dietary sugar reduction is one therapeutic strategy for improving nonalcoholic fatty liver disease (NAFLD), and the underlying mechanisms for this effect warrant further investigation. Here, we employed metabolomics and metagenomics to examine systemic biological adaptations associated with dietary sugar restriction and (subsequent) hepatic fat reductions in youth with NAFLD. Data/samples were from a randomized controlled trial in adolescent boys (11–16 years, mean ± SD: 13.0 ± 1.9 years) with biopsy-proven NAFLD who were either provided a low free-sugar diet (LFSD) ( n = 20) or consumed their usual diet ( n = 20) for 8 weeks. Plasma metabolomics was performed on samples from all 40 participants by coupling hydrophilic interaction liquid chromatography (HILIC) and C 18 chromatography with mass spectrometry. In a sub-sample ( n = 8 LFSD group and n = 10 usual diet group), 16S ribosomal RNA (rRNA) sequencing was performed on stool to examine changes in microbial composition/diversity. The diet treatment was associated with differential expression of 419 HILIC and 205 C 18 metabolite features ( p < 0.05), which were enriched in amino acid pathways, including methionine/cysteine and serine/glycine/alanine metabolism ( p < 0.05), and lipid pathways, including omega-3 and linoleate metabolism ( p < 0.05). Quantified metabolites that were differentially changed in the LFSD group, compared to usual diet group, and representative of these enriched metabolic pathways included increased serine ( p = 0.001), glycine ( p = 0.004), 2-aminobutyric acid ( p = 0.012), and 3-hydroxybutyric acid ( p = 0.005), and decreased linolenic acid ( p = 0.006). Microbiome changes included an increase in richness at the phylum level and changes in a few genera within Firmicutes . In conclusion, the LFSD treatment, compared to usual diet, was associated with metabolome and microbiome changes that may reflect biological mechanisms linking dietary sugar restriction to a therapeutic decrease in hepatic fat. Studies are needed to validate our findings and test the utility of these “omics” changes as response biomarkers.

CITATION EXPORT

Catherine C. Cohen, Helaina Huneault, Carolyn J. Accardi et al.. Metabolome × Microbiome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys. Metabolites. (2023). https://doi.org/10.3390/metabo13030401

AUTHORS

11 · 10 CENTRES

Catherine C. Cohen, Helaina Huneault, Carolyn J. Accardi, Dean P. Jones, Ken Liu, Kristal M. Maner-Smith, Ming Song, Jean A. Welsh, Patricia A. Ugalde-Nicalo, Jeffrey B. Schwimmer, Miriam B. Vos

1Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
2Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA
3Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA
4Emory Integrated Lipidomics Core, School of Medicine, Emory University, Atlanta, GA 30322, USA
5Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA
6Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
7Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA
8Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
9Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, CA 92123, USA
10Department of Pediatrics, School of Medicine, University of California, San Diego, CA 92093, USA

EDITOR / REVIEWER

Kuen-Cheh Yang, Tsung-Po Chen