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 (P-FDR<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 x 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.