Stool metabolome-microbiota evaluation among children and adolescents with obesity, overweight, and normal-weight using 1H NMR and 16S rRNA gene profiling

José Diógenes Jaimes,Andrea Slavíčková,Ondřej Cinek,Jaroslav Havlík,Jakub Hurych,Karel Černý,Lucie Vodolánová,Ben Nichols,Suzanne L Ishaq

doi:10.1371/journal.pone.0247378

José Diógenes Jaimes, Andrea Slavíčková + Show 7 more

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https://doi.org/10.1371/journal.pone.0247378

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Abstract

Characterization of metabolites and microbiota composition from human stool provides powerful insight into the molecular phenotypic difference between subjects with normal weight and those with overweight/obesity. The aim of this study was to identify potential metabolic and bacterial signatures from stool that distinguish the overweight/obesity state in children/adolescents. Using 1H NMR spectral analysis and 16S rRNA gene profiling, the fecal metabolic profile and bacterial composition from 52 children aged 7 to 16 was evaluated. The children were classified into three groups (16 with normal-weight, 17 with overweight, 19 with obesity). The metabolomic analysis identified four metabolites that were significantly different (p < 0.05) among the study groups based on one-way ANOVA testing: arabinose, butyrate, galactose, and trimethylamine. Significantly different (p < 0.01) genus-level taxa based on edgeR differential abundance tests were genus Escherichia and Tyzzerella subgroup 3. No significant difference in alpha-diversity was detected among the three study groups, and no significant correlations were found between the significant taxa and metabolites. The findings support the hypothesis of increased energy harvest in obesity by human gut bacteria through the growing observation of increased fecal butyrate in children with overweight/obesity, as well as an increase of certain monosaccharides in the stool. Also supported is the increase of trimethylamine as an indicator of an unhealthy state.

Highlights

The proportion of children and adolescents aged 5 to 19 considered overweight has risen globally from approximately 1 in 10 in the mid-1970s to about to about 1 in 5 in 2016 [1]
At the phylum level, a high Firmicutes/ Bacteroidetes ratio has been associated with obesity [6,7,8], and even specific strains such as F. prausnitzii have been positively correlated with body mass index (BMI) z-score [8]
Given that the diet among the participants in our study was, except for portion size (OW and OB consumed, on average, 30% fewer kcal than N), approximately homogenous, it does suggest higher microbial fermentation activity from fermentative substrates such as resistant starch and dietary fiber, the main sources of microbiota-derived short-chain fatty acid (SCFA) [5, 8, 44]

Summary

Introduction

The proportion of children and adolescents aged 5 to 19 considered overweight has risen globally from approximately 1 in 10 in the mid-1970s to about to about 1 in 5 in 2016 [1]. There is strong evidence of a close relationship between childhood overweight/obesity and multiple comorbidities which, collectively, reduce life expectancy and increase mortality. This has become an emerging public health problem that has attracted the wide attention of researchers [2,3,4]. Identifying potential biomarkers in pediatric populations via metabolomics and 16S rDNA profiling can provide an opportunity to identify these conditions, but to find potential prevention and treatment approaches. Despite inter-individual differences, approaches using 16S rRNA gene amplicon sequencing (16S rDNA profiling) of fecal samples have shown differing gut bacterial composition between children with obesity and those without [5]. Microbiome studies have far tended to focus on adult populations; compositional and functional differences between children and adult cohorts have not been reported [11]

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