Metabolomic profiling of stool of two-year old children from the INSIGHT study reveals links between butyrate and child weight outcomes

Background Metabolomic analysis is commonly used to understand the biological underpinning of diseases such as obesity. However, our knowledge of gut metabolites related to weight outcomes in young children is currently limited. Objectives To (1) explore the relationships between metabolites and child weight outcomes, (2) determine the potential effect of covariates (e.g., child's diet, maternal health/habits during pregnancy, etc.) in the relationship between metabolites and child weight outcomes, and (3) explore the relationship between selected gut metabolites and gut microbiota abundance. Methods Using H-1-NMR, we quantified 30 metabolites from stool samples of 170 two-year-old children. To identify metabolites and covariates associated with children's weight outcomes (BMI [weight/height(2)], BMI z-score [BMI adjusted for age and sex], and growth index [weight/height]), we analysed the H-1-NMR data, along with 20 covariates recorded on children and mothers, using LASSO and best subset selection regression techniques. Previously characterized microbiota community information from the same stool samples was used to determine associations between selected gut metabolites and gut microbiota. Results At age 2 years, stool butyrate concentration had a significant positive association with child BMI (p-value = 3.58 x 10(-4)), BMI z-score (p-value = 3.47 x 10(-4)), and growth index (p-value = 7.73 x 10(-4)). Covariates such as maternal smoking during pregnancy are important to consider. Butyrate concentration was positively associated with the abundance of the bacterial genus Faecalibacterium (p-value = 9.61 x 10(-3)). Conclusions Stool butyrate concentration is positively associated with increased child weight outcomes and should be investigated further as a factor affecting childhood obesity.