Gut Microbiome

Integrated multi-omics analysis reveals distinct metabolic signatures and gut microbiome alterations across the pediatric obesity spectrum.

TL;DR

In 57 Mexican children, integrated liver enzyme, fecal and serum metabolomic, and 16S gut microbiome analyses showed distinct metabolic and microbial signatures across the obesity spectrum, identifying GGT as a sensitive pediatric metabolic biomarker and pointing to SCFA, bile acid, tryptophan-indole and aromatic amino acid pathways as mechanistic links and potential therapeutic targets.

Key Findings

Gamma-glutamyl transferase (GGT) showed the strongest association with obesity among the liver enzymes measured.

  • GGT was 25.5 ± 6.0 U/L in obese children vs. 15.0 ± 3.0 U/L in normal-weight children (p < 0.001).
  • The authors report that GGT outperformed ALT and AST as an early hepatic stress biomarker.
  • The cohort comprised 57 Mexican children: normal weight (n = 15), overweight (n = 8), obese (n = 34).

Demographic parameters were comparable across BMI groups, which limits confounding.

  • The abstract reports comparability across groups (p = 0.632).
  • Groups were stratified by BMI into NW, Ow, and Ob.

Untargeted metabolomics identified large numbers of altered fecal and serum metabolites in obese vs. normal-weight children.

  • 1088 fecal and 1041 serum metabolites were altered (Ob vs. NW).
  • Enriched pathways included aromatic amino acid metabolism, one-carbon metabolism, glycolysis/TCA cycle, and nucleotide biosynthesis.

Specific metabolite perturbations in obesity included upregulation of kynurenine and 3-nitrotyrosine and downregulation of bile acids and purine metabolites.

  • These were highlighted as key perturbations in Ob vs. NW comparisons.
  • The changes span tryptophan/aromatic amino acid metabolism, oxidative/nitrosative stress, bile acid, and purine pathways.

16S rRNA sequencing revealed numerous differentially abundant taxa between BMI groups and greater beta-diversity dispersion in obesity.

  • 78 differentially abundant taxa in Ow vs. NW, 95 in Ob vs. Ow, and 28 in Ob vs. NW.
  • Beta-diversity dispersion was elevated in obesity.

Co-abundance network analysis showed disrupted metabolite-metabolite and taxon-taxon interactions in obesity.

  • Findings included loss of beneficial SCFA-producing consortia.
  • Bile acid dysregulation and altered amino acid-microbiome coupling were also observed.

Integrating microbiome and metabolome data revealed high-magnitude genus-metabolite correlations.

  • Lachnospiraceae correlated with acetate (ρ = 0.92).
  • Tyzzerella correlated with vulpecholate (ρ = 0.94).
  • Correlations mapped to pathways linking SCFAs, bile acids, tryptophan-indole derivatives, and aromatic amino acids to obesity pathogenesis.

The study also included antimicrobial resistance assessment alongside liver enzyme profiling, metabolomics, and microbiome sequencing as part of a multi-omics design.

  • Methods listed: liver enzyme profiling, untargeted fecal and serum metabolomics, 16S rRNA sequencing, and antimicrobial resistance assessment.
  • The abstract does not report specific antimicrobial resistance results.

What This Means

This study looked at 57 Mexican children, grouped as normal weight, overweight, or obese, to see how obesity relates to liver blood tests, the chemicals (metabolites) in stool and blood, and the bacteria living in the gut. The groups were similar in basic demographics, so differences are less likely to be due to age or sex. Of the liver tests, gamma-glutamyl transferase (GGT) was most clearly higher in children with obesity (about 25.5 vs. 15.0 U/L in normal-weight children), and the authors suggest it may be a more sensitive early warning sign of liver stress than the more commonly used ALT and AST. Children with obesity also had over a thousand differences in stool and blood metabolites, affecting pathways involved in amino acid handling, energy metabolism, bile acids, and purines. Gut bacteria also differed between groups, with signs of lost beneficial short-chain-fatty-acid-producing bacteria and disrupted bacterial and chemical networks. This research suggests that obesity in childhood is linked to coordinated changes in gut bacteria and body chemistry, and that GGT might be a useful marker for early metabolic stress. The study is small, particularly the overweight group (8 children), and shows correlations rather than cause and effect, so the proposed therapeutic targets would need testing in larger and longer studies.

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Citation

Arredondo-Hernandez R, Ordu&#xf1;a P, Schcolnik-Cabrera A, Castillo-Rojas G, L&#xf3;pez-Filloy M, Morales-Nava P, et al.. (2026). Integrated multi-omics analysis reveals distinct metabolic signatures and gut microbiome alterations across the pediatric obesity spectrum.. Gut microbes. https://doi.org/10.1080/19490976.2026.2755119