Environmental and intrinsic factors shaping gut microbiota composition and diversity and its relation to metabolic health in children and early adolescents: A population-based study.

BACKGROUND: Gut microbiota, by influencing multiple metabolic processes in the host, is an important determinant of human health and disease. However, gut dysbiosis associated with metabolic complications shows inconsistent patterns. This is likely driven by factors shaping gut microbial composition that have largely been under-evaluated, at a population level, in school-age children, especially from developing countries. RESULTS: Through characterization, by 16S sequencing, of the largest gut microbial population-based school-aged children cohort in Latin America (ORSMEC, N = 926, aged 6-12 y), we identified associations of 14 clinical and environmental covariates (PFDR<0.1), collectively explaining 15.7% of the inter-individual gut microbial variation. Extrinsic factors such as markers of socioeconomic status showed a major influence in the most abundant taxa and in the enterotypes' distribution. Age was positively correlated with higher diversity, but only in normal-weight children (rho = 0.138, P =2 × 10-3). In contrast, this correlation although not significant, was negative in overweight and obese children (rho = -0.125, P = 0.104 and rho = -0.058, P = 0.409, respectively). Finally, co-abundance groups (CAGs) were associated with the presence of metabolic complications. CONCLUSIONS: Our study offers evidence that the presence of overweight and obesity could impair the microbial diversity maturation associated with age. Furthermore, it provides novel results toward a better understanding of gut microbiota in the pediatric population that will ultimately help to develop therapeutic approaches to improve metabolic status.

An Amino Acid Signature Associated with Obesity Predicts 2-Year Risk of Hypertriglyceridemia in School-Age Children.

Childhood obesity is associated with a number of metabolic abnormalities leading to increased cardiovascular risk. Metabolites can be useful as early biomarkers and new targets to promote early intervention beginning in school age. Thus, we aimed to identify metabolomic profiles associated with obesity and obesity-related metabolic traits. We used data from the Obesity Research Study for Mexican children (ORSMEC) in Mexico City and included a case control (n = 1120), cross-sectional (n = 554) and a longitudinal study (n = 301) of 6-12-year-old children. Forty-two metabolites were measured using electrospray MS/MS and multivariate regression models were used to test associations of metabolomic profiles with anthropometric, clinical and biochemical parameters. Principal component analysis showed a serum amino acid signature composed of arginine, leucine/isoleucine, phenylalanine, tyrosine, valine and proline significantly associated with obesity (OR = 1.57; 95%CI 1.45-1.69, P = 3.84 × 10-31) and serum triglycerides (TG) (ß = 0.067, P = 4.5 × 10-21). These associations were validated in the cross-sectional study (P < 0.0001). In the longitudinal cohort, the amino acid signature was associated with serum TG and with the risk of hypertriglyceridemia after 2 years (OR = 1.19; 95%CI 1.03-1.39, P = 0.016). This study shows that an amino acid signature significantly associated with childhood obesity, is an independent risk factor of future hypertriglyceridemia in children.