Are all Breastfed Infants Equal? Clustering Metabolomics Data to Identify Predictive Risk Clusters for Childhood Obesity.

OBJECTIVE

Fetal and early life represent a period of developmental plasticity during which metabolic pathways are modified by environmental and nutritional cues. Little is known on the pathways underlying this multifactorial complex. We explored whether 6 months old breastfed infants could be clustered into metabolically similar groups and that those metabotypes could be used to predict later obesity risk.

METHODS

Plasma samples were obtained from 183 breastfed infants aged 6-months participating in the European multicenter Childhood Obesity Project study. We measured amino acids along with polar lipid concentrations (acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins). We determined the metabotypes using a Bayesian agglomerative clustering method and investigated the properties of these clusters with respect to clinical, programming, and metabolic factors up to 6 years of age.

RESULTS

We identified 20 metabolite clusters comprising 1-39 children. Phosphatidylcholines predominantly influenced the clustering process. In the largest clusters (n ≥ 14), large differences existed for birth length (unadjusted P < 0.0001) and length and weight at 6 months (unadjusted P < 0.0001 and P = 0.012, respectively). Infants tended to cluster together by country (unadjusted P < 0.001). The BMI z-score at 6 years of age tended to differ (unadjusted P = 0.07).

CONCLUSIONS

Our exploratory study provided evidence that breastfed infants are not metabolically homogeneous and that variation in metabolic profiles among infants might provide insight into later development and health. This work highlights the potential of metabotypes for identifying inter-individual differences that may form the basis for developing personalized early preventive strategies.