400 - Comparing Gut Microbiome Metagenomic and Metabolomic Signatures of Children With and Without Obesity

Adult studies report gut microbiome taxonomic changes and metabolomic signatures correlated to obesity, but few studies explore these functional profiles among children with obesity. Correlating distinct signatures in childhood may elucidate their relationship to early cardiometabolic disease promotion and/or mitigation.

Objective: To compare the fecal microbiome, metagenomics, and metabolomic profiles of children with and without obesity.

Design/Methods: This is a cross-sectional analysis of previously collected fecal samples from 71 children, ages 5-12 years old, without (HW) and with class 1, 2, 3 obesity (OB1, OB2, OB3 categorized by CDC LMS method). The metabolites were assayed by liquid chromatograph-mass spectrometry using an untargeted approach, then quantified and annotated using the Human Metabolome Database. Metagenomic shotgun libraries were constructed and sequenced using NovaSeq 6000 S4 flow cell. Comparisons among categories (HW/OB1,2,3) were performed for metabolites using orthogonal partial least squares discriminant analysis (OPDL-SA) and for microbiome composition using principal coordinate analysis (PCoA), LEfSe, and MaAsLin2.  Metagenomic analysis used KEGG and MetaCyc pathway databases. Most correlations used general linear models.  

Results:

Children had a mean (SD) age 9.6(2.3) years, with 52% White, 56% male, and 46% had OB2/OB3 with higher BMI z-scores for Black females (p=0.02). OPDL-SA of >22,000 compounds revealed 3 correlating with OB3 vs. HW with 1 identified as 10-Propoxy-decanoic acid, a fatty acid. Adjusted PCoA models showed no significant genus/species level correlations, but relative abundant species correlations by LEfSe. Alistipes finegoldii was negatively correlated with OB3. Further metagenomic pathway/metabolite analysis revealed significant correlations of aspartate kinase expression within amino acid metabolism and negative correlations of 4 pathways to short chain fatty acids and OB3 (r= -0.4 to -0.52).

Conclusion(s):

Untargeted metabolomic and metagenomic analysis generated correlations to severe childhood obesity. As examples, 10-Propoxy-decanoic acid has a strong inhibitory effect on glycerol 3 phosphate acyltransferase (GPAT) which promotes obesity, fatty liver disease and insulin resistance, and Alistipes finegoldii is associated with glucose tolerance and anti-obesity effects. The biological significance of pathways and OB3/SCFA correlations as well as species’ functional role in promotion/mitigation of cardiometabolic conditions is not clear in this analysis. Further studies are needed to interpret the biological significance of these findings.