Gut microbiome and obesity in late adolescence: a case-control study in "Children of 1997" birth cohort

Ann Epidemiol. 2024 Dec 20:S1047-2797(24)00280-1. doi: 10.1016/j.annepidem.2024.12.009. Online ahead of print.

Abstract

Purpose: Although the gut microbiome is important in human health, its relation to adolescent obesity remains unclear. Here we assessed the associations of the gut microbiome with adolescent obesity in a case-control study.

Methods: In the "Children of 1997" birth cohort, participants with and without obesity at ~17.4 years were 1:1 matched on sex, physical activity, parental education and occupation (n=312). Fecal gut microbiome composition and pathways were assessed via shotgun metagenomic sequencing. The association of microbiota species with obesity was evaluated using conditional logistic regression. We explored the association of the obesity-relevant species with adolescent metabolomics using multivariable linear regression, and causal relationships with type 2 diabetes using Mendelian randomization analysis.

Results: Gut microbiota in the adolescents with obesity exhibited lower richness (p=0.031) and evenness (p=0.014) compared to controls. Beta diversity revealed differences in the microbiome composition in two groups (p=0.034). Lower relative abundance of Clostridium spiroforme, Clostridium phoceensis and Bacteroides uniformis were associated with higher obesity risk (q<0.15). Lower Bacteroides uniformis was associated with higher branched-chain amino acid, potentially contributing to higher type 2 diabetes risk.

Conclusion: Adolescents with obesity had a distinct gut microbiota profile compared to the controls, possibly linked to metabolic pertubation and related diseases.

Keywords: Gut microbiome; Mendelian Randomization; adolescent obesity; case-control study; metabolomics.